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Dang-Tan, Tam, Shiyuan Zhang, Ruben V. Tavares, Melissa Stutz, Afisi S. Ismaila, Julie Vaillancourt, Diane Corriveau, et al. "The Burden of Illness Related to Chronic Obstructive Pulmonary Disease Exacerbations in Québec, Canada." Canadian Respiratory Journal 2017 (2017): 1–10. http://dx.doi.org/10.1155/2017/8184915.
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Background. Chronic obstructive pulmonary disease (COPD) prevalence in Canada has risen over time. COPD-related exacerbations contribute to the increased health care utilization (HCU) in this population. This study investigated the impact of exacerbations on COPD-related HCU. Methods. This retrospective observational cohort study used patient data from the Québec provincial health insurance databases. Eligible patients with a new HCU claim with a diagnostic billing for COPD during 2001–2010 were followed until March 31, 2011. Exacerbation rates and time to first exacerbation were assessed. Unadjusted analyses and multivariable models compared the rate of HCU by exacerbation classification (any [moderate/severe], moderate, or severe). Results. The exacerbation event rate in patients with an exacerbation was 34.3 events/100 patient-years (22.7 for moderate exacerbations and 11.6 for severe exacerbations). Median time to first exacerbation of any classification was 37 months. In unadjusted analyses, COPD-related HCU significantly increased with exacerbation severity. In the multivariable, HCU rates were significantly higher after exacerbation versus before exacerbation (p<0.01) for patients with an exacerbation or moderate exacerbations. For severe exacerbations, general practitioner, respiratory specialist, emergency room, and hospital visits were significantly higher after exacerbation versus before exacerbation (p<0.001). Conclusions. Exacerbations were associated with increased HCU, which was more pronounced for patients with severe exacerbations. Interventions to reduce the risk of exacerbations in patients with COPD may reduce disease burden.
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Krachunov, Iliya, Nikolay Kyuchukov, Zlatina Ivanova, Nikolay A. Yanev, Petkana A. Hristova, Plamen Pavlov, Pavlina Glogovska, Tsanya Popova, and Yavor Y. Ivanov. "Stability of Frequent Exacerbator Phenotype in Patients with Chronic Obstructive Pulmonary Disease." Folia Medica 60, no. 4 (December 1, 2018): 536–45. http://dx.doi.org/10.2478/folmed-2018-0023.
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Abstract Background: At present, there is little information in Bulgaria regarding the rate and stability of frequent-exacerbation phenotype in COPD patients. Aim: To study the rate and stability of frequent-exacerbation phenotype in COPD patients. Materials and methods: We followed up 465 COPD patients for exacerbations over a 3-year period. Exacerbations were defined as events that resulted in treatment with antibiotics and/or corticosteroids (moderate), or that led to hospitalization (severe). Result: Approximately 10% of the patients had two or more exacerbations per year (frequent-exacerbation phenotype), and this structure stayed stable over the study period. The exacerbation rate in the first year of follow up was 0.33 per stage I COPD patients (according to GOLD stages), 0.49 per stage II COPD patients; 0.69 - for stage III, and 1.06 for stage IV COPD patients. The frequent-exacerbation rate increased from stage I to stage IV by 4.35%, 9.17%, 10.79%, and 20.97%, respectively. A history of previous year exacerbations increased the risk of new exacerbations: with a history of one exacerbation - OR 2.1820 (95% CI: 1.4018 to 3.3965, p = 0.0005), and with a history of two exacerbations - OR 4.6460 (95% CI: 2.3286 to 9.2696; p < 0.0001). The frequent-exacerbation phenotype appeared to be unstable over the study period - up to 33% from those patients stayed in the phenotype for the next year. Conclusions: The exacerbation frequency and the rate of frequent-exacerbation phenotype increases with COPD progression. History of exacerbations in the previous year is a significant risk factor for exacerbations of COPD. The frequent-exacerbation phenotype appeared to be unstable over the study period. The pheno-type of non-exacerbators was more likely to remain stable over time.
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Mayhew, David, Nathalie Devos, Christophe Lambert, James R. Brown, Stuart C. Clarke, Viktoriya L. Kim, Michal Magid-Slav, et al. "Longitudinal profiling of the lung microbiome in the AERIS study demonstrates repeatability of bacterial and eosinophilic COPD exacerbations." Thorax 73, no. 5 (January 31, 2018): 422–30. http://dx.doi.org/10.1136/thoraxjnl-2017-210408.
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BackgroundAlterations in the composition of the lung microbiome associated with adverse clinical outcomes, known as dysbiosis, have been implicated with disease severity and exacerbations in COPD.ObjectiveTo characterise longitudinal changes in the lung microbiome in the AERIS study (Acute Exacerbation and Respiratory InfectionS in COPD) and their relationship with associated COPD outcomes.MethodsWe surveyed 584 sputum samples from 101 patients with COPD to analyse the lung microbiome at both stable and exacerbation time points over 1 year using high-throughput sequencing of the 16S ribosomal RNA gene. We incorporated additional lung microbiology, blood markers and in-depth clinical assessments to classify COPD phenotypes.ResultsThe stability of the lung microbiome over time was more likely to be decreased in exacerbations and within individuals with higher exacerbation frequencies. Analysis of exacerbation phenotypes using a Markov chain model revealed that bacterial and eosinophilic exacerbations were more likely to be repeated in subsequent exacerbations within a subject, whereas viral exacerbations were not more likely to be repeated. We also confirmed the association of bacterial genera, including Haemophilus and Moraxella, with disease severity, exacerbation events and bronchiectasis.ConclusionsSubtypes of COPD have distinct bacterial compositions and stabilities over time. Some exacerbation subtypes have non-random probabilities of repeating those subtypes in the future. This study provides insights pertaining to the identification of bacterial targets in the lung and biomarkers to classify COPD subtypes and to determine appropriate treatments for the patient.Trial registration numberResults, NCT01360398.
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Sadatsafavi, Mohsen, Don D. Sin, Zafar Zafari, Gerard Criner, John E. Connett, Stephen Lazarus, Meilan Han, Fernando Martinez, and Richard Albert. "The Association Between Rate and Severity of Exacerbations in Chronic Obstructive Pulmonary Disease: An Application of a Joint Frailty-Logistic Model." American Journal of Epidemiology 184, no. 9 (November 1, 2016): 681–89. http://dx.doi.org/10.1093/aje/kww085.
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Abstract Exacerbations are a hallmark of chronic obstructive pulmonary disease (COPD). Evidence suggests the presence of substantial between-individual variability (heterogeneity) in exacerbation rates. The question of whether individuals vary in their tendency towards experiencing severe (versus mild) exacerbations, or whether there is an association between exacerbation rate and severity, has not yet been studied. We used data from the MACRO Study, a 1-year randomized trial of the use of azithromycin for prevention of COPD exacerbations (United States and Canada, 2006–2010; n = 1,107, mean age = 65.2 years, 59.1% male). A parametric frailty model was combined with a logistic regression model, with bivariate random effects capturing heterogeneity in rate and severity. The average rate of exacerbation was 1.53 episodes/year, with 95% of subjects having a model-estimated rate of 0.47–4.22 episodes/year. The overall ratio of severe exacerbations to total exacerbations was 0.22, with 95% of subjects having a model-estimated ratio of 0.04–0.60. We did not confirm an association between exacerbation rate and severity (P = 0.099). A unified model, implemented in standard software, could estimate joint heterogeneity in COPD exacerbation rate and severity and can have applications in similar contexts where inference on event time and intensity is considered. We provide SAS code (SAS Institute, Inc., Cary, North Carolina) and a simulated data set to facilitate further uses of this method.
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Soenjoyo, Karina Ruth, Nivedita Nadkarni, and Mariko Siyue Koh. "Comparison of exacerbation phenotypes among patients with severe asthma." Allergy and Asthma Proceedings 41, no. 4 (July 1, 2020): e67-e79. http://dx.doi.org/10.2500/aap.2020.41.200029.
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Background: Exacerbation phenotypes among patients with severe asthma have been largely characterized during stable periods. Little is known about severe asthma patients during exacerbation periods. Objective: To compare persistently frequent exacerbators (PFE), non‐persistently frequent exacerbators (NPFE), and infrequent exacerbators (IFE) among patients with severe asthma during stable and exacerbation periods. Methods: Patients with severe asthma who were admitted for asthma exacerbations from 2011 to 2017 and on follow up at Singapore General Hospital were recruited and categorized as PFEs (two or more exacerbations per year over 2 consecutive years), NPFEs (two or more exacerbations in 1 year only), or IFEs (fewer than two exacerbations per year over 2 consecutive years). Demographic, clinical, and laboratory data were collected at baseline and during exacerbation periods. Results: The participants were categorized as the following: 20 PFEs, 36 NPFEs, and 57 IFEs, with no significant demographic differences. The participants as PFEs (versus NPFEs and IFEs) were characterized by having a higher prevalence of psychiatric disorders (25% versus 8% versus 5%; p = 0.046), more comorbidities (7 versus 4 versus 2; p < 0.001), and a higher steroid burden per year (1150 versus 456 versus 350 mg; p < 0.001). The participants who were PFEs (versus IFEs) had a higher total immunoglobulin E (IgE) level (625 versus 232 IU/mL; p = 0.046) and longer duration of admission stay (3 versus 2 days; p = 0.009). All three groups had higher blood neutrophil counts during exacerbation periods than during stable periods (p = 0.008 versus p < 0.001 versus p = 0.004). Conclusion: The participants categorized as PFEs were characterized by comorbidities, higher steroid burden, IgE levels, and longer hospital stays. Exacerbations in the participants with severe asthma, regardless of exacerbation phenotype, were characterized by neutrophilia. These findings provided insights into potential therapeutic strategies to reduce exacerbations in patients with severe asthma.
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Nault, Diane, Maria F. Sedano, Lorena Soto, Alexandre Joubert, Isabelle Drouin, and Jean Bourbeau. "A Model Applied to a Real Life Situation: Self-Management with a Written Action Plan for Early Treatment of COPD Exacerbations." Clinical & Investigative Medicine 30, no. 3 (June 1, 2007): 44. http://dx.doi.org/10.25011/cim.v30i3.1750.
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Background: We hypothesized that self-management education with the use of a written action plan provided by a nurse case manager can help patients to gain the proper skills to start an early treatment for an acute exacerbation.
Methods: COPD patients from an outpatient clinic with access to a written action plan and self-administered prescription were instructed to initiate their antibiotics and/or prednisone in case of exacerbation, and call their nurse case manager for supervision. The following data was collected: symptoms change, patients delay in taking action to treat their exacerbations (starting antibiotics and prednisone, calling the case manager) and use of hospital services.
Results: We report on 187 exacerbations occurring in a cohort of 113 moderate / severe COPD patients with FEV1 of 37 ± 16% predicted (mean ± SD). 161 exacerbations were supervised by the case manager at the time of the event. The remaining 26 exacerbations were detected after the event. 87% of the supervised exacerbations presented with 2 major symptoms (increased dyspnea, increased sputum volume and/or purulent sputum). Patient’s delay to initiate treatment in supervised exacerbations was 2.04 ± 1.8 days; 85% took action to treat the exacerbation within 3 days. The treatment for supervised and unsupervised exacerbations was similar (slightly more antibiotics and prednisone were used for unsupervised ones) and they had similarly favourable outcomes in terms of health services use, with 68.5% of the exacerbations not requiring any hospital services.
Conclusions: Patients can take an active role, acquire the skills to recognize exacerbation symptoms and start an early treatment of antibiotics and prednisone according to the directives of their written action plan.
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El Sawy, Ihab H., Reham M. Wagdy, Afaf G. Ibrahim, and Suzy W. Ibrahim. "Risk factors associated with severe asthma exacerbations in children attending Alexandria University Children’s Hospital, Egypt." International Journal Of Community Medicine And Public Health 5, no. 12 (November 24, 2018): 5019. http://dx.doi.org/10.18203/2394-6040.ijcmph20184670.
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Background: Severe asthma exacerbation is one of the common pediatric medical emergencies that necessitates hospital visits. The study aimed to identify risk factors associated with pediatric severe asthma exacerbations that might have the potential to guide the parents for early medical consultations and physicians at primary health care centers for proper management.Methods: A case-control study was conducted on over 100 asthmatic children below 12 years attending the Emergency Department of Alexandria University Children’s Hospital in acute exacerbation. Based on a modified pulmonary index score, the patients were allocated into 2 groups; study group (50 patients with severe asthma exacerbation) and control group (50 patients with mild asthma exacerbations). Demographic data, history of illness, alarming clinical signs, medications, and outcome of all participants were recorded.Results: Severe asthma exacerbations were more encountered among males, older age, and with a longer duration of asthma (X±SD=28.4±15.9 months) with significant differences when compared to controls. Comparing the studied groups revealed higher risk for severe asthma exacerbations mainly with; history of sudden onset of severe respiratory distress (Odds ratio “OR”=30.13, 95% CI, 13.78-66.69) and chronic steroid-dependent asthma (OR=14.46, 95% CI, 3.97-52.65). Cyanosis, lethargy, and inability to talk were alarming signs in patients with severe asthma exacerbation when compared to those with mild asthma exacerbation (p<0.05).Conclusions: Severe asthma exacerbation in children is still associated with many risk factors that may alert the patients’ caregivers and physicians prospectively for early proper management.
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FitzGerald, J. Mark, Peter J. Barnes, Bradley E. Chipps, Christine R. Jenkins, Paul M. O'Byrne, Ian D. Pavord, and Helen K. Reddel. "The burden of exacerbations in mild asthma: a systematic review." ERJ Open Research 6, no. 3 (July 2020): 00359–2019. http://dx.doi.org/10.1183/23120541.00359-2019.
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BackgroundAlthough most patients with asthma have mild disease, data on how mild asthma is defined, and how frequently exacerbations occur in this patient population are scarce, so we aimed to redress this.MethodsWe searched Medline and Medline In-Process (PubMed), and Embase in OVID for English-language publications containing “mild asthma” plus at least one relevant therapy and outcome/keyword, limited to randomised controlled trials (RCTs) and observational studies published between January 1990 and February 2019. Publications were filtered to ensure appropriate data extraction. The main outcomes were the definitions of mild asthma and exacerbations, baseline exacerbation rates and exacerbation data for placebo recipients in prospective studies. Meta-analysis of exacerbation rates was planned.FindingsOf 4064 articles identified, 64 were included in our review (49 743 subjects); 54 RCTs and 10 observational/other studies. Six main types of definitions of mild asthma were identified. While care was taken to ensure inclusion only of patients with mild asthma, marked heterogeneity was revealed in the definitions of mild asthma and hence the study populations. Reporting of exacerbations also varied widely between studies, precluding meta-analysis. Between 0–22% of patients were hospitalised for asthma or had a severe exacerbation in the previous year, according to baseline data from prospective studies. In RCTs, severe exacerbation rates in placebo recipients taking only short-acting β2-agonist therapy ranged from 0.20–2.88 per year.ConclusionsThese data provide new evidence of the burden of exacerbations in mild asthma and highlight the need for standardised definitions of mild asthma and of exacerbations to progress further research.
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Matsuse, Hiroto, Tomoko Tsuchida, Susumu Fukahori, Tetsuya Kawano, Shinya Tomari, Nobuko Matsuo, Tomoya Nishino, Chizu Fukushima, and Shigeru Kohno. "Retrospective Cohort Study of Leukotriene Receptor Antagonist Therapy for Preventing Upper Respiratory Infection-Induced Acute Asthma Exacerbations." Allergy & Rhinology 4, no. 3 (January 2013): ar.2013.4.0062. http://dx.doi.org/10.2500/ar.2013.4.0062.
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Upper respiratory tract infections (URIs) represent the most frequent cause of acute asthma exacerbations. It has yet to be determined whether leukotriene receptor antagonist (LTRA) treatment prevents URI-induced acute asthma exacerbations in adults. The objective of the present study was to evaluate the preventive effects of LTRA treatment on URI-induced acute asthma exacerbations. The incidences of URI alone, acute asthma exacerbation without URI, and URI-induced acute asthma exacerbation were determined retrospectively by analyzing diary and medical records of 321 adult asthmatic patients (mean age, 56.3 ± 17.2 years; male/female ratio, 117:204) over 1 year. Results were compared between patients who had been taking an LTRA (n = 137) and those who had never taken any LTRA (n = 184) during the study periods. Significantly fewer URIs alone and acute asthma exacerbations without URI occurred in patients with than in those without prophylactic daily use of LTRA. LTRA treatment significantly reduced the durations of URIs alone and of total acute asthma exacerbations, as well as the incidence of mild exacerbations of asthma. In contrast, in patients with URI-induced acute asthma exacerbations, LTRA treatment failed to significantly reduce the interval between URI onset and acute asthma exacerbation, as well as the duration and severity of both URIs and acute asthma exacerbations. Use of an LTRA for adult asthmatic patients appears to reduce the incidences of URIs alone and acute asthma exacerbations without URI, but it failed to prevent URI-induced acute asthma exacerbations once a URI occurred.
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Nurhayati, Dewi, Ida Parwati, Tiene Rostini, and Arto Yuwono. "KADAR SURFACTANT PROTEIN-D SERUM PADA PASIEN PENYAKIT PARU OBSTRUKTIF KRONIS BERKEBAHAYAAN KAMBUHAN RENDAH DAN TINGGI." INDONESIAN JOURNAL OF CLINICAL PATHOLOGY AND MEDICAL LABORATORY 22, no. 2 (March 27, 2018): 168. http://dx.doi.org/10.24293/ijcpml.v22i2.1122.
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Chronic obstructive pulmonary disease (COPD) cause high morbidity and mortality worldwide. The exacerbations in chronicobstructive pulmonary disease accelerate the decline in lung function and health status, as well as in increasing the treatment cost andmortality risk. The spiro metric measurement has several limitations in assessing the severity as well as the exacerbation risk in COPDpatients. Currently, has been available serum surfactant protein-D, a marker of lung inflammation and lung tissue damage. This proteinis produced by the alveolar type II cells and the Clara cells that play role in maintaining the lung stability and pulmonary immunesystem. The increased level of serum SPD indicates that there is lung epitihelial leakage in line with COPD severity increment and reflectedin COPD exacerbation level of risk according to combined COPD assessment GOLD criteria of the year 2011. The aim of this study wasto know the differences of SP-D serum levels between low and high risk of exacerbation in COPD patients by determination them. Thisstudy was conducted from March to July 2014. The subjects of this study were COPD patients diagnosed by spiro metric measurement.The research was conducted in comparative analytic way with a cross sectional study design. The statistical analysis was performedusing Mann-Whitney non-parametric test. The subjects were 62 COPD patients. The SP-D serum level at low risk of exacerbation groupdiffer significantly compared to the high risk exacerbation group, 1.8–68.4 ng/mL and 3.36–116.4 ng/mL respectively (P=0.018).Based on this study it can be concluded that the SP-D serum levels were higher in COPD patients with high risk exacerbation than thelower risk one. The SP-D serum levels may be considered as a specific marker of lung tissue injury to assess the risk of the exacerbationin COPD patients.
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Reechaipichitkul, Wipa. "Precipitating causes and outcomes of chronic obstructive pulmonary disease exacerbation at a tertiary care center in northeast Thailand." Asian Biomedicine 8, no. 2 (April 1, 2014): 229–36. http://dx.doi.org/10.5372/1905-7415.0802.283.
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Abstract Background: Acute exacerbation of chronic obstructive pulmonary disease (COPD) is a leading cause of hospitalization and economic burden. Frequent exacerbations impair quality of life and effect decline of lung function. Objective: We evaluated characteristics of COPD patients with frequent exacerbations. The precipitating causes, outcomes, hospital stay, and cost of admission were also determined. Methods: The study population included COPD patients admitted because of acute COPD exacerbation at Srinagarind Hospital between 1 January 2006 and 31 December 2010. Results: Over the 5-year period, 183 patients were admitted. Their mean age was 74.9 (SD 9.28) years and the male to female ratio was 170:13. Most patients (144; 79%) had one exacerbation per year and 39 (21%) had more than one per year. The group with more exacerbations, had a higher stage of the disease than those with only one exacerbation (p = 0.023), but there was no significant difference in the mortality rate (18% vs 14%, p = 0.53). A total of 245 episodes of acute exacerbation of COPD occurred in 183 patients. The mean duration of symptoms was 4.1 (SD 3.46) days. Forty-seven percent presented with Anthonisen type III, 42.4% with Anthonisen type II, and 10.6% with Anthonisen type I exacerbations. For 44 exacerbations (18%), the precipitating causes were not determined. The most common precipitating cause was pneumonia, which occurred in 90 episodes (36.7%). The second common was bronchitis (27.8%); followed by heart failure (8.2%), infected bronchiectasis (5.3%), diarrhea (1.2%), acute urinary retention (0.8%), unstable angina (0.4%), pneumothorax (0.4%), urinary tract infection (0.4%), atrial fibrillation (0.4%) and drug induced cough (0.4%). The organisms responsible for respiratory tract infection were identified in 31% cases of pneumonia and 18% of bronchitis cases. The top three common pathogens for pneumonia were Pseudomonas aeruginosa (9%), Acinetobacter baumannii (8%), and Klebsiella pneumoniae (8%). The top three common pathogens for bronchitis were P aeruginosa (7%), Haemophilus influenza (6%), and K pneumoniae (4%). About one quarter (25.3%) of acute exacerbations were complicated by respiratory failure. The mean duration of admission was 17.3 days (range 1-682 days). The mean cost of admission per exacerbation was 80,010 Thai baht (US $2,666) (range, 2,779-3,433,108 baht). The total cost for 245 exacerbations was 19.6 million baht ($653,000). Conclusion: Respiratory tract infections were common causes of COPD exacerbation and one quarter of which developed respiratory failure. Preventive measures such as vaccination, smoking cessation, lung rehabilitation, and appropriate drug use are helpful.
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Greenberger, Paul A. "Lessons learned from clinical trials of asthma." Allergy and Asthma Proceedings 40, no. 6 (November 1, 2019): 410–13. http://dx.doi.org/10.2500/aap.2019.40.4259.
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Exacerbations of persistent or intermittent asthma should be anticipated by physicians and health-care professionals. Patients who are likely to experience an exacerbation often have a history of an exacerbation in the previous year, and the absolute eosinophil count in peripheral blood is ≥ 400/μL. Similarly, expectorated or induced sputum eosinophilia of ≥2% is associated with exacerbations. These phenotypic findings have led to effective biologic therapies, which target eosinophils or immunoglobulin E or the T-helper type 2 phenotype, especially in children, adolescents, and adults with frequent exacerbations. In children, a reduced forced expiratory volume in the first second of expiration (FEV1) to forced vital capacity ratio can be associated with future exacerbations, although the FEV1 may be in the normal range, even with children who have persistent severe asthma. Asthma control questionnaires did not differentiate between children with or children without a future exacerbation. Alternatively, in adults, the lower baseline FEV1 (2.3 L [74% predicted] versus 2.5 L [78% predicted]) identified patients more likely to have a future exacerbation compared with patients who were not having an exacerbation. After correcting for FEV1, the asthma control questionnaire data were associated with exacerbations. In adolescents (ages ≥ 12 years) and adults with persistent mild asthma, most (73%) did not have sputum eosinophilia, and some of these patients responded well to the anticholinergic, tiotropium, which would argue differently from administration of an inhaled corticosteroid as first-line controller therapy. In a three-track study of patients with persistent mild asthma, as-needed budesonide-formoterol and scheduled budesonide were associated with approximately one-half of the annual exacerbation rate of as-needed albuterol. In patients with persistent moderate-to-severe asthma, tiotropium added to controller therapy caused an increase in FEV1 without improving the asthma control questionnaire findings. There were two studies that explored whether either quadrupling or quintupling the inhaled corticosteroid at the first sign of loss of control of asthma would provide meaningful reductions of severe exacerbations of asthma, but the findings did not support this strategy. Both biologic therapies and environmental control (dust mite impermeable encasings) have resulted in reductions of exacerbations in patients with persistent moderate and severe asthma.
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Wilkinson, Tom M. A., Emmanuel Aris, Simon C. Bourne, Stuart C. Clarke, Mathieu Peeters, Thierry G. Pascal, Laura Taddei, et al. "Drivers of year-to-year variation in exacerbation frequency of COPD: analysis of the AERIS cohort." ERJ Open Research 5, no. 1 (February 2019): 00248–2018. http://dx.doi.org/10.1183/23120541.00248-2018.
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The association between exacerbation aetiology and exacerbation frequency is poorly understood.We analysed 2-year follow-up data from a prospective observational study of patients with chronic obstructive pulmonary disease (COPD) (www.clinicaltrials.gov identifier number NCT01360398) to evaluate year-to-year variation in exacerbation frequency and related aetiology. A total of 127 patients underwent blood and sputum sampling monthly and at exacerbation to detect respiratory infections and eosinophilic inflammation; 103 continued into year 2 and 88 completed both years.The most common bacterial species at stable state and exacerbation was Haemophilus influenzae. Among infrequent exacerbators (one exacerbation per year), the incidence of viral infection at exacerbation was high (60.0% (95% CI 35.1–81.7%) in year 1 and 78.6% (53.4–94.2%) in year 2). Those with more frequent exacerbations tended to have higher relative incidence of bacterial than viral infection. Patients with at least two additional exacerbations in year 2 versus year 1 had a higher risk of H. influenzae colonisation at stable state than those with at least two fewer exacerbations, as detected by culture (OR 1.43 (95% CI 0.71–2.91) versus 0.63 (0.40–1.01), p=0.06) and PCR (1.76 (95% CI 0.88–3.51) versus 0.56 (0.37–0.86), p<0.01). This was not seen with other infection types or eosinophilic inflammation.Analysis of the same cohort over 2 years showed, for the first time, that changes in yearly COPD exacerbation rate may be associated with variations in H. influenzae colonisation.
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Karimi, Leila, Lies Lahousse, Mohsen Ghanbari, Natalie Terzikhan, André G. Uitterlinden, Johan van der Lei, Guy G. Brusselle, Bruno H. Stricker, and Katia M. C. Verhamme. "β2-Adrenergic Receptor (ADRB2) Gene Polymorphisms and Risk of COPD Exacerbations: The Rotterdam Study." Journal of Clinical Medicine 8, no. 11 (November 1, 2019): 1835. http://dx.doi.org/10.3390/jcm8111835.
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The role of the β2-adrenergic receptor (ADRB2) gene in patients with chronic obstructive pulmonary disease (COPD) is unclear. We investigated the association between ADRB2 variants and the risk of exacerbations in COPD patients treated with inhaled β2-agonists. Within the Rotterdam Study, a population-based cohort study, we followed 1,053 COPD patients until the first COPD exacerbation or end of follow-up and extracted rs1042713 (16Arg > Gly) and rs1042714 (27Gln > Glu) in ADRB2. Exposure to inhaled β2-agonists was categorised into current, past or non-use on the index date (date of COPD exacerbation for cases and on the same day of follow-up for controls). COPD exacerbations were defined as acute episodes of worsening symptoms requiring systemic corticosteroids and/or antibiotics (moderate exacerbations), or hospitalization (severe exacerbations). The associations between ADRB2 variants and COPD exacerbations were assessed using Cox proportional hazards models, adjusting for age, sex, use of inhaled corticosteroids, daily dose of β2-agonists, and smoking. In current users of β2-agonists, the risk of COPD exacerbation decreased by 30% (hazard ratio (HR); 0.70, 95% CI: 0.59–0.84) for each copy of the Arg allele of rs1042713 and by 20% (HR; 0.80, 95% CI: 0.69–0.94) for each copy of the Gln allele of rs1042714. Furthermore, current users carrying the Arg16/Gln27 haplotype had a significantly lower risk (HR; 0.70, 95% CI: 0.59–0.85) of COPD exacerbation compared to the Gly16/Glu27 haplotype. In conclusion, we observed that the Arg16/Gln27 haplotype in ADRB2 was associated with a reduced risk of COPD exacerbation in current users of inhaled β2-agonists.
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Singer, Florian, Anne Schlegtendal, Sylvia Nyilas, François Vermeulen, Mieke Boon, and Cordula Koerner-Rettberg. "Lung clearance index predicts pulmonary exacerbations in individuals with primary ciliary dyskinesia: a multicentre cohort study." Thorax 76, no. 7 (January 27, 2021): 681–88. http://dx.doi.org/10.1136/thoraxjnl-2020-215504.
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BackgroundLung clearance index (LCI) is a promising lung function outcome in individuals with primary ciliary dyskinesia (PCD). The impact of events clinically important for individuals with PCD, such as pulmonary exacerbations, on LCI is unknown.MethodsWe conducted an international, multicentre, observational cohort study to assess the association of LCI and risk of pulmonary exacerbation, specific changes in LCI during pulmonary exacerbation and global variability of LCI across four visits every 4 months. Ninety individuals with PCD, aged 3–41 years, underwent nitrogen multiple-breath washout (MBW) and spirometry measurements. The association of LCI and pulmonary exacerbations was assessed by Cox proportional hazards and random-effects regression models.ResultsWe obtained 430 MBW and 427 spirometry measurements. In total, 379 person-years at risk contributed to the analysis. Per one unit increase (deterioration) in LCI, the risk of future pulmonary exacerbation increased by 13%: HR (95% CI), 1.13 (1.04 to 1.23). If LCI changed from a range of values considered normal to abnormal, the risk of future pulmonary exacerbations increased by 87%: 1.87 (1.08 to 3.23). During pulmonary exacerbations, LCI increased by 1.22 units (14.5%). After pulmonary exacerbations, LCI tended to decline. Estimates of variability in LCI suggested lower variation within individuals compared with variation between individuals. Findings were comparable for forced expiratory volume in 1 s.ConclusionOn a visit-to-visit basis, LCI measurement may add to the prediction of pulmonary exacerbations, the assessment of lung function decline and the potential lung function response to treatment of pulmonary exacerbations.
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de Roos, Emmely W., Lies Lahousse, Katia M. C. Verhamme, Gert-Jan Braunstahl, Johannes J. C. C. M. in ‘t Veen, Bruno H. Stricker, and Guy G. O. Brusselle. "Incidence and predictors of asthma exacerbations in middle-aged and older adults: the Rotterdam Study." ERJ Open Research 7, no. 3 (April 29, 2021): 00126–2021. http://dx.doi.org/10.1183/23120541.00126-2021.
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AimThe aim of this study was to investigate occurrence and determinants of asthma exacerbations in an ageing general population.MethodsSubjects aged 45 years or above with physician-diagnosed asthma in the Rotterdam Study, a population-based prospective cohort from January 1991 to May 2018, were assessed for asthma exacerbations. Exacerbations were defined as acute episodes of worsening asthma treated with oral corticosteroids. Cox proportional hazards analysis was used to investigate risk factors for a future exacerbation.ResultsOut of 763 participants with asthma (mean age 61.3 years, 69.2% female), 427 (56.0%) experienced at least one exacerbation, in a mean follow-up time of 13.9 years. The mean annual exacerbation rate was 0.22. Most exacerbations occurred during winter months. Risk factors for exacerbations were a history of previous exacerbations (HR 4.25; 95% CI 3.07–5.90, p<0.001)), respiratory complaints (HR 2.18; 95% CI 1.48–3.21, p<0.001), airflow obstruction (HR 1.52; 95% CI 1.07–2.15, p=0.019), obesity (HR 1.38; 95% CI 1.01–1.87, p=0.040) and depressive symptoms (HR 1.55; 95% CI 1.05–2.29, p=0.027). Compared to those not using respiratory medication, we observed higher hazard ratios for those on short-acting β2-agonists (SABA, i.e. rescue medication) only (HR 3.08, 95% CI 1.61–5.90, p=0.001) than those on controller medication (HR 2.50, 95% CI 1.59–3.92, p<0.001).ConclusionMany older adults with asthma suffer from at least one severe exacerbation. Previous exacerbations, use of SABA without concomitant controller medication, respiratory complaints, obesity, airway obstruction and depression are independent risk factors for exacerbations.
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Chen, Ching-Yi, Wang-Chun Chen, Chi-Hsien Huang, Yi-Ping Hsiang, Chau-Chyun Sheu, Yung-Che Chen, Meng-Chih Lin, Kuo-An Chu, Cheng-Hung Lee, and Yu-Feng Wei. "LABA/LAMA fixed-dose combinations versus LAMA monotherapy in the prevention of COPD exacerbations: a systematic review and meta-analysis." Therapeutic Advances in Respiratory Disease 14 (January 2020): 175346662093719. http://dx.doi.org/10.1177/1753466620937194.
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Background: Long-acting muscarinic antagonist (LAMA) monotherapy is recommended for chronic obstructive pulmonary disease (COPD) patients with high risk of exacerbations. It is unclear whether long-acting β2-agonist (LABA)/LAMA fixed-dose combinations (FDCs) are more effective than LAMAs alone in preventing exacerbations. The aim of this study was to systematically review the literature to investigate whether LABA/LAMA FDCs are more effective than LAMA monotherapy in preventing exacerbations. Methods: We searched several databases and manufacturers’ websites to identify relevant randomized clinical trials comparing LABA/LAMA FDC treatment with LAMAs alone ⩾24 weeks. Outcomes of interest were time to first exacerbation and rates of moderate to severe, severe and all exacerbations. Results: We included 10 trials in 9 articles from 2013 to 2018 with a total of 19,369 patients for analysis in this study. Compared with LAMA monotherapy, LABA/LAMA FDCs demonstrated similar efficacy in terms of time to first exacerbation [hazard ratio, 0.96; 95% confidence interval (CI) 0.79–1.18; p = 0.71], moderate to severe exacerbations [risk ratio (RR), 0.96; 95% CI 0.90–1.03; p = 0.28], severe exacerbations (RR, 0.92; 95% CI 0.81–1.03; p = 0.15), and a marginal superiority in terms of all exacerbations (RR, 0.92; 95% CI 0.86–1.00; p = 0.04). The incidence of all exacerbation events was lower in the LABA/LAMA FDC group for the COPD patients with a history of previous exacerbations and those with a longer treatment period (52–64 weeks). Conclusion: This study provides evidence that LABA/LAMA FDCs are marginally superior in the prevention of all exacerbations compared with LAMA monotherapy in patients with COPD. The reviews of this paper are available via the supplemental material section.
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Collard, Harold R., Luca Richeldi, Dong Soon Kim, Hiroyuki Taniguchi, Inga Tschoepe, Maurizio Luisetti, Jesse Roman, et al. "Acute exacerbations in the INPULSIS trials of nintedanib in idiopathic pulmonary fibrosis." European Respiratory Journal 49, no. 5 (May 2017): 1601339. http://dx.doi.org/10.1183/13993003.01339-2016.
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Time to first investigator-reported acute exacerbation was a key secondary end-point in the INPULSIS trials of nintedanib in patients with idiopathic pulmonary fibrosis (IPF).We used the INPULSIS trial data to investigate risk factors for acute exacerbation of IPF and to explore the impact of nintedanib on risk and outcome of investigator-reported and adjudicated confirmed/suspected acute exacerbations. Mortality following these events and events adjudicated as not acute exacerbations was analysed using the log rank test.Risk of acute exacerbations was most strongly associated with the following variables: baseline forced vital capacity (higher risk with lower value), baseline supplemental oxygen (higher risk with use), baseline antacid medication (higher risk with use), treatment (higher risk with placebo), and for confirmed/suspected acute exacerbations, cigarette smoking. Mortality was similar following investigator-reported and adjudicated confirmed/suspected acute exacerbations. Nintedanib had no significant effect on risk of mortality post-exacerbation.Investigator-reported acute exacerbations of IPF are associated with similar risk factors and outcomes as adjudicated confirmed/suspected acute exacerbations.
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Vestbo, Jørgen, and Peter Lange. "Prevention of COPD exacerbations: medications and other controversies." ERJ Open Research 1, no. 1 (May 2015): 00011–2015. http://dx.doi.org/10.1183/23120541.00011-2015.
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Exacerbations have significant impact on the morbidity and mortality of patients with chronic obstructive pulmonary disease. Most guidelines emphasise prevention of exacerbations by treatment with long-acting bronchodilators and/or anti-inflammatory drugs. Whereas most of this treatment is evidence-based, it is clear that patients differ regarding the nature of exacerbations and are likely to benefit differently from different types of treatment. In this short review, we wish to highlight this, suggest a first step in differentiating pharmacological exacerbation prevention and call for more studies in this area. Finally, we wish to highlight that there are perhaps easier ways of achieving similar success in exacerbation prevention using nonpharmacological tools.
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Al Rajeh, Ahmed M., Yousef Saad Aldabayan, Abdulelah Aldhahir, Elisha Pickett, Shumonta Quaderi, Jaber S. Alqahtani, Swapna Mandal, Marc CI Lipman, and John R. Hurst. "Once Daily Versus Overnight and Symptom Versus Physiological Monitoring to Detect Exacerbations of Chronic Obstructive Pulmonary Disease: Pilot Randomized Controlled Trial." JMIR mHealth and uHealth 8, no. 11 (November 13, 2020): e17597. http://dx.doi.org/10.2196/17597.
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Background Earlier detection of chronic obstructive pulmonary disease (COPD) exacerbations may facilitate more rapid treatment with reduced risk of hospitalization. Changes in pulse oximetry may permit early detection of exacerbations. We hypothesized that overnight pulse oximetry would be superior to once-daily monitoring for the early detection of exacerbations. Objective This study aims to evaluate whether measuring changes in heart rate and oxygen saturation overnight is superior to once-daily monitoring of both parameters and to assess symptom changes in facilitating earlier detection of COPD exacerbations. Methods A total of 83 patients with COPD were randomized to once-daily or overnight pulse oximetry. Both groups completed the COPD assessment test questionnaire daily. The baseline mean and SD for each pulse oximetry variable were calculated from 14 days of stable monitoring. Changes in exacerbation were expressed as Z scores from this baseline. Results The mean age of the patients was 70.6 (SD 8.1) years, 52% (43/83) were female, and the mean FEV1 was 53.0% (SD 18.5%) predicted. Of the 83 patients, 27 experienced an exacerbation. Symptoms were significantly elevated above baseline from 5 days before to 12 days after treatment initiation. Day-to-day variation in pulse oximetry during the stable state was significantly less in the overnight group than in the once-daily group. There were greater relative changes at exacerbation in heart rate than oxygen saturation. An overnight composite score of change in heart rate and oxygen saturation changed significantly from 7 days before initiation of treatment for exacerbation and had a positive predictive value for exacerbation of 91.2%. However, this was not statistically better than examining changes in symptoms alone. Conclusions Overnight pulse oximetry permits earlier detection of COPD exacerbations compared with once-daily monitoring. Monitoring physiological variables was not superior to monitoring symptoms, and the latter would be a simpler approach, except where there is a need for objective verification of exacerbations. Trial Registration ClinicalTrials.gov NCT03003702; https://clinicaltrials.gov/ct2/show/NCT03003702
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Kim, Viktoriya L., Ngaire A. Coombs, Karl J. Staples, Kristoffer K. Ostridge, Nicholas P. Williams, Stephen A. Wootton, Jeanne-Marie Devaster, et al. "Impact and associations of eosinophilic inflammation in COPD: analysis of the AERIS cohort." European Respiratory Journal 50, no. 4 (October 2017): 1700853. http://dx.doi.org/10.1183/13993003.00853-2017.
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Eosinophilic inflammation in chronic obstructive pulmonary disease (COPD) predicts response to treatment, especially corticosteroids. We studied the nature of eosinophilic inflammation in COPD prospectively to examine the stability of this phenotype and its dynamics across exacerbations, and its associations with clinical phenotype, exacerbations and infection.127 patients aged 40–85 years with moderate to very severe COPD underwent repeated blood and sputum sampling at stable visits and within 72 h of exacerbation for 1 year.Blood eosinophils ≥2% was prevalent at baseline, and predicted both predominantly raised stable-state eosinophils across the year (area under the curve 0.841, 95% CI 0.755–0.928) and increased risk of eosinophilic inflammation at exacerbation (OR 9.16; p<0.001). Eosinophils ≥2% at exacerbation and eosinophil predominance at stable visits were associated with a lower risk of bacterial presence at exacerbation (OR 0.49; p=0.049 and OR 0.25; p=0.065, respectively). Bacterial infection at exacerbation was highly seasonal (winter versus summer OR 4.74; p=0.011) in predominantly eosinophilic patients.Eosinophilic inflammation is a common and stable phenotype in COPD. Blood eosinophil counts in the stable state can predict the nature of inflammation at future exacerbations, which when combined with an understanding of seasonal variation provides the basis for the development of new treatment paradigms for this important condition.
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Tsvetkova, О. A., and O. O. Voronkova. "The value of the medicine fenoterol + ipratropium bromide in the treatment of exacerbations of bronchial asthma and chronic obstructive pulmonary disease." Meditsinskiy sovet = Medical Council, no. 17 (November 22, 2020): 35–39. http://dx.doi.org/10.21518/2079-701x-2020-17-35-39.
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The purpose of the article is to determine the place of the combined bronchodilator fenoterol + ipratropium bromide in the treatment of exacerbations of bronchial asthma, COPD and recommendations on various delivery methods. The treatment of exacerbations of bronchial asthma (BA) and chronic obstructive pulmonary disease (COPD) is of interest to a general practitioner. Although this concept has lost most of its gloomy colors in the last decade thanks to the new concept of diagnosing and treating patients, the problem of providing qualified timely assistance at the time of an exacerbation remains acute and not always solvable. Often the basis for the treatment of exacerbation of asthma and COPD is repeated administration of a fast-acting inhaled short-acting b2-agonist or an anticholinergic drug, or their combination, early administration of systemic corticosteroids and oxygen inhalation. Exacerbation therapy should be as safe as possible for patients. Following the recommendations for the treatment of asthma and COPD exacerbations both on an outpatient basis and in a hospital can significantly reduce the frequency of asthma and COPD exacerbations. Medical care that a patient can receive at home depends on the experience of the physician and the patient, as well as on the possibilities of medicine and instrumental provision. Ideally, the level of peak expiratory flow (PEF) should be a measure of control over one’s well-being, both in remission and in an exacerbation.
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Fernaays, Matthew M., Alan J. Lesse, Sanjay Sethi, Xueya Cai, and Timothy F. Murphy. "Differential Genome Contents of Nontypeable Haemophilus influenzae Strains from Adults with Chronic Obstructive Pulmonary Disease." Infection and Immunity 74, no. 6 (June 2006): 3366–74. http://dx.doi.org/10.1128/iai.01904-05.
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ABSTRACT Haemophilus influenzae is an important cause of otitis media in children and lower respiratory infection in adults with chronic obstructive pulmonary disease (COPD). Patients with COPD experience periodic exacerbations that are associated with acquisition of new bacterial strains. However, not every strain acquisition is associated with exacerbation. To test the hypothesis that genetic differences among strains account for differences in pathogenic potential, a microarray consisting of 4,992 random 1.5- to 3-kb genomic fragments of an exacerbation strain was constructed. Competitive hybridization was performed using six strains associated with exacerbation as well as five strains associated with asymptomatic colonization. Seven sequences that were absent in all five colonization strains and present in at least two exacerbation strains were identified. One such sequence was a previously unreported gene with high homology to the meningococcal immunoglobulin A (IgA) protease gene, which is distinct from the previously described H. influenzae IgA protease. To assess the distribution of the seven sequences among well-characterized strains of H. influenzae, 59 exacerbation strains and 73 asymptomatic colonization strains were screened by PCR for the presence of these sequences. The presence or absence of any single sequence was not significantly associated with exacerbations of COPD. However, logistic regression and subgroup analysis identified combinations of the presence and absence of genes that are associated with exacerbations. These results indicate that patterns of genes are associated with the ability of strains of H. influenzae to cause exacerbations of COPD, supporting the concept that differences in pathogenic potential are based in part on genomic differences among infecting strains, not merely host factors.
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Xiao, Wei, Long-yi Du, Bing Mao, Ti-wei Miao, and Juan-juan Fu. "Endotype-driven prediction of acute exacerbations in chronic obstructive pulmonary disease (EndAECOPD): protocol for a prospective cohort study." BMJ Open 9, no. 11 (November 2019): e034592. http://dx.doi.org/10.1136/bmjopen-2019-034592.
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IntroductionCurrent strategies for the prevention of acute exacerbations in chronic obstructive pulmonary disease (COPD) are primarily based on clinical measurements but fail to target the pathophysiological mechanisms, namely endotypes, of the disease. Studies identifying endotypes underlying exacerbation susceptibility and discovering specific biomarkers may lead to the development of targeted therapeutics but are lacking. This study aims to assess a broad spectrum of biomarkers at multiple biological levels (genetics, airway inflammation and respiratory microbiome) for their ability in predicting acute exacerbations of COPD, thus enables high-resolution disease endotyping and may lead to precision treatment of the disease.Methods and analysisIn this prospective cohort study, participants with stable COPD (n=600) will be recruited and assessed for demographics, symptom scores, spirometry, medication use and comorbidities at baseline. Blood will be obtained for genotyping variants in a panel of nine genes. Induced sputum will be collected for the profile of microbiota using 16S rRNA gene sequencing, quantification of bacterial load, inflammatory mediators assay and sputum cytometry. Participants will be followed up for their exacerbations till 12 months and reassessed for the clinical measurements as baseline. The primary outcomes are total number of exacerbations, severe exacerbations, moderate exacerbations and time to first exacerbation. The secondary outcomes are changes in lung function and symptom scores. The effect of biomarkers representing genetic variants, airway inflammation and respiratory microbiome on predicting the frequent exacerbator phenotype and exacerbation frequency will be analysed with multivariable modelling, and time to first exacerbation with a Cox regression model.Ethics and disseminationThe study has been approved by the Clinical Trial and Biomedical Ethics Committee of West China Hospital of Sichuan University (No. 2018–298). The results of the study will be published on peer-reviewed journals.Trial registration numberChiCTR1800019063.
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Dal Negro, Roberto W., Jadwiga A. Wedzicha, Martin Iversen, Giovanni Fontana, Clive Page, Arrigo F. Cicero, Edoardo Pozzi, and Peter M. A. Calverley. "Effect of erdosteine on the rate and duration of COPD exacerbations: the RESTORE study." European Respiratory Journal 50, no. 4 (October 2017): 1700711. http://dx.doi.org/10.1183/13993003.00711-2017.
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Oxidative stress contributes to chronic obstructive pulmonary disease (COPD) exacerbations and antioxidants can decrease exacerbation rates, although we lack data about the effect of such drugs on exacerbation duration.The RESTORE (Reducing Exacerbations and Symptoms by Treatment with ORal Erdosteine in COPD) study was a prospective randomised, double-blind, placebo-controlled study, enrolling patients aged 40–80 years with Global Initiative for Chronic Obstructive Lung Disease stage II/III. Patients received erdosteine 300 mg twice daily or placebo added to usual COPD therapy for 12 months. The primary outcome was the number of acute exacerbations during the study.In the pre-specified intention-to-treat population of 445 patients (74% male; mean age 64.8 years, forced expiratory volume in 1 s 51.8% predicted) erdosteine reduced the exacerbation rate by 19.4% (0.91 versus. 1.13 exacerbations·patient−1·year−1 for erdosteine and placebo, respectively; p=0.01), due to an effect on mild events; the reduction in the rate of mild exacerbations was 57.1% (0.23 versus 0.54 exacerbations·patient−1·year−1 for erdosteine and placebo, respectively; p=0.002). No significant difference was observed in the rate of moderate and severe exacerbations (0.68 versus 0.59 exacerbations·patient−1·year−1 for erdosteine and placebo, respectively; p=0.054) despite a trend in favour of the comparison group. Erdosteine decreased the exacerbation duration irrespective of event severity by 24.6% (9.55 versus 12.63 days for erdosteine and placebo, respectively; p=0.023). Erdosteine significantly improved subject and physician subjective severity scores (p=0.022 and p=0.048, respectively), and reduced the use of reliever medication (p<0.001), but did not affect the St George's Respiratory Questionnaire score or the time to first exacerbation.In patients with COPD, erdosteine can reduce both the rate and duration of exacerbations. The percentage of patients with adverse events was similar in both the placebo and erdosteine treatment groups.
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Salem, Ahmed, Heng Zhong, Mafalda Ramos, Mark Lamotte, and Hao Hu. "Potential clinical and economic impact of optimised maintenance therapy on discharged patients with COPD after hospitalisation for an exacerbation in China." BMJ Open 11, no. 4 (April 2021): e043664. http://dx.doi.org/10.1136/bmjopen-2020-043664.
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ObjectivesChronic obstructive pulmonary disease (COPD) exacerbations requiring hospitalisation are a considerable burden, both clinically and economically. Although long-acting maintenance therapy is recommended in both the GOLD (Global Initiative for Chronic Obstructive Lung Disease) and Chinese COPD guidelines, proper implementation is lacking. The objective of this study was to assess the clinical and economic impact of prescribing long-acting maintenance therapy to discharged patients with COPD after hospitalisation for an exacerbation in China by using an outcomes model.DesignThis health economic analysis was conducted using a Markov cohort model from the Chinese healthcare payer perspective. Two health states (alive and dead) were modelled, and exacerbations were included as possible events.SettingThe target population was Chinese patients with COPD, >40 years of age, who were hospitalised for an exacerbation, with 1 year of follow-up. A recent COPD national prevalence study was referenced for population calculations.InterventionA hypothetical future scenario, where 100% of patients would receive long-acting maintenance therapy after hospitalisation for an exacerbation, was compared with the current scenario, in which only 38.5% of patients are receiving long-acting maintenance therapy after hospitalisation.Outcome measuresNumber of exacerbations, deaths and medical costs were measured.ResultsWe estimated that there were approximately 4 million Chinese patients with COPD who were hospitalised annually due to an exacerbation. By prescribing long-acting maintenance therapy, our model predicted that 917 360 exacerbations and 4034 deaths could be avoided, translating into cost savings of ¥3.5 billion (US$0.5 billion). Scenario analysis also showed that if the rate of exacerbations requiring hospitalisation was higher than our base case analysis, cost savings could reach up to ¥10.7 billion (US$1.5 billion).ConclusionAdministering long-acting maintenance therapy to more patients with COPD at hospital discharge could considerably reduce exacerbations and healthcare spending in China.
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Li, A. K., M. Barton, J. A. Delport, and D. Ashok. "Edwardsiella tardaInfection Triggering Acute Relapse in Pediatric Crohn’s Disease." Case Reports in Infectious Diseases 2019 (March 20, 2019): 1–3. http://dx.doi.org/10.1155/2019/2094372.
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Crohn’s disease exacerbations can often be associated with bacterial infections causing gastroenteritis. We report a child who experienced exacerbation of his Crohn’s disease associated with a positive stool culture forEdwardsiella tarda (E. tarda). Endoscopy showed features of moderate inflammation similar to exacerbation of Crohn’s disease. The patient was treated simultaneously with intravenous steroids and antibiotics, and his symptoms resolved. This case report highlights the importance of clinicians being able to promptly recognize and treat concurrent bacterial infections in Crohn’s disease exacerbations.
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Mohr, David C., Stacey L. Hart, Laura Julian, Darcy Cox, and Daniel Pelletier. "Association between stressful life events and exacerbation in multiple sclerosis: a meta-analysis." BMJ 328, no. 7442 (March 19, 2004): 731. http://dx.doi.org/10.1136/bmj.38041.724421.55.
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AbstractObjective To quantify the association between stressful life events and exacerbations of multiple sclerosis.Data sources PubMed, PsychInfo, and Psychological Abstracts searched for empirical papers from 1965 to February 2003 with terms “stress”, “trauma”, and “multiple sclerosis”.Review methods Three investigators independently reviewed papers for inclusion/exclusion criteria and extracted the relevant data, including methods, sample statistics, and outcomes.Results Of 20 studies identified, 14 were included. The meta-analysis showed a significant increase in risk of exacerbation in multiple sclerosis after stressful life events, with a weighted average effect size of d = 0.53 (95% confidence interval 0.40 to 0.65), P < 0.0001. The studies were homogenous, q = 16.62, p = 0.22, i2 = 21.8%. Neither sampling nor study methods had any effect on study outcomes.Conclusions There is a consistent association between stressful life events and subsequent exacerbation in multiple sclerosis. However these data do not allow the linking of specific stressors to exacerbations nor should they be used to infer that patients are responsible for their exacerbations. Investigation of the psychological, neuroendocrine, and immune mediators of stressful life events on exacerbation may lead to new behavioural and pharmacological strategies targeting potential links between stress and exacerbation.
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Cheng, Shih-Lung, Kuo-Chin Chiu, Hsin-Kuo Ko, Diahn-Warng Perng, Hao-Chien Wang, Chong-Jen Yu, Chau-Chyun Sheu, Sheng-Hao Lin, and Ching-Hsiung Lin. "Comparing Patient Characteristics, Clinical Outcomes, and Biomarkers of Severe Asthma Patients in Taiwan." Biomedicines 9, no. 7 (July 1, 2021): 764. http://dx.doi.org/10.3390/biomedicines9070764.
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Purpose: To understand the association between biomarkers and exacerbations of severe asthma in adult patients in Taiwan. Materials and Methods: Demographic, clinical characteristics and biomarkers were retrospectively collected from the medical charts of severe asthma patients in six hospitals in Taiwan. Exacerbations were defined as those requiring asthma-specific emergency department visits/hospitalizations, or systemic steroids. Enrolled patients were divided into: (1) those with no exacerbations (non-exacerbators) and (2) those with one or more exacerbations (exacerbators). Receiver operating characteristic curves were used to determine the optimal cut-off value for biomarkers. Generalized linear models evaluated the association between exacerbation and biomarkers. Results: 132 patients were enrolled in the study with 80 non-exacerbators and 52 exacerbators. There was no significant difference in demographic and clinical characteristics between the two groups. Exacerbators had significantly higher eosinophils (EOS) counts (367.8 ± 357.18 vs. 210.05 ± 175.24, p = 0.0043) compared to non-exacerbators. The optimal cut-off values were 292 for EOS counts and 19 for the Fractional exhaled Nitric Oxide (FeNO) measure. Patients with an EOS count ≥ 300 (RR = 1.88; 95% CI, 1.26–2.81; p = 0.002) or FeNO measure ≥ 20 (RR = 2.10; 95% CI, 1.05–4.18; p = 0.0356) had a significantly higher risk of exacerbation. Moreover, patients with both an EOS count ≥ 300 and FeNO measure ≥ 20 had a significantly higher risk of exacerbation than those with lower EOS count or lower FeNO measure (RR = 2.16; 95% CI, 1.47–3.18; p = < 0.0001). Conclusions: Higher EOS counts and FeNO measures were associated with increased risk of exacerbation. These biomarkers may help physicians identify patients at risk of exacerbations and personalize treatment for asthma patients.
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Stolk, Jan, Naveh Tov, Kenneth R. Chapman, Pablo Fernandez, William MacNee, Nicholas S. Hopkinson, Eeva Piitulainen, et al. "Efficacy and safety of inhaled α1-antitrypsin in patients with severe α1-antitrypsin deficiency and frequent exacerbations of COPD." European Respiratory Journal 54, no. 5 (August 29, 2019): 1900673. http://dx.doi.org/10.1183/13993003.00673-2019.
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Patients with inherited α1-antitrypsin (AAT) deficiency (ZZ-AATD) and severe chronic obstructive pulmonary disease (COPD) frequently experience exacerbations. We postulated that inhalation of nebulised AAT would be an effective treatment.We randomly assigned 168 patients to receive twice-daily inhalations of 80 mg AAT solution or placebo for 50 weeks. Patients used an electronic diary to capture exacerbations. The primary endpoint was time from randomisation to the first event-based exacerbation. Secondary endpoints included change in the nature of the exacerbation as defined by the Anthonisen criteria. Safety was also assessed.Time to first moderate or severe exacerbation was a median of 112 days (interquartile range (IQR) 40–211 days) for AAT and 140 days (IQR 72–142 days) for placebo (p=0.0952). The mean yearly rate of all exacerbations was 3.12 in the AAT-treated group and 2.67 in the placebo group (p=0.31). More patients receiving AAT reported treatment-related treatment-emergent adverse events compared to placebo (57.5% versus 46.9%, respectively) and they were more likely to withdraw from the study. After the first year of the study, when modifications to the handling of the nebuliser were introduced, the rate of safety events in the AAT-treated group dropped to that of the placebo group.We conclude that in AATD patients with severe COPD and frequent exacerbations, AAT inhalation for 50 weeks showed no effect on time to first exacerbation but may have changed the pattern of the episodes.
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Maliavko, Natalia S., Nikita O. Shatyi, Elena V. Alagova, Marina A. Pokhaznikova, and Anatoliy K. Lebedev. "Detection of exacerbactions of chronic obstructive lung disease in the ambulatory practice." Russian Family Doctor 22, no. 1 (March 15, 2018): 18–22. http://dx.doi.org/10.17816/rfd2018118-22.
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The article presents the results of a retrospective study aimed at identifying exacerbations in outpatients with chronic obstructive pulmonary disease (COPD) during the previous 12 months. А telephone interview was conducted with 20 patients with COPD from the departments of general medical practice of three polyclinics in the Kalininsky district of St. Petersburg. The obtained data were compared with records in outpatient cards to determine the presence of registered cases of appeals to the polyclinic for exacerbation of the disease.7 patients (35%) were identified retrospectively using the questionnaire, which can be attributed to the phenotype of COPD with frequent exacerbations. Among them, five people were hospitalized in a hospital for exacerbation of COPD, and two patients had 2 or more exacerbations in an outpatient card that did not lead to hospitalization. In 5 patients (33%), among those who were not in hospital for an exacerbation of COPD for the previous 12 months, indirect signs of low self-esteem were revealed, indicating that it is necessary to raise awareness of the exacerbation of COPD and the education patients self-management skills. (For citation: Maliavko NS, Shatyi NO, Alagova EV, et al. Detection of exacerbactions of chronic obstructive lung disease in the ambulatory practice. Russian Family Doctor. 2018;22(1):18-22. doi 10.17816/RFD2018118-22).
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Rong, Yiran, John P. Bentley, Gerald McGwin, Yi Yang, Benjamin F. Banahan, Sara L. Noble, Terri Kirby, and Sujith Ramachandran. "Association Between Transient Opioid Use and Short-Term Respiratory Exacerbation Among Adults With Chronic Obstructive Pulmonary Disease: A Case-Crossover Study." American Journal of Epidemiology 188, no. 11 (August 30, 2019): 1970–76. http://dx.doi.org/10.1093/aje/kwz169.
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Abstract The association of historical opioid use with health care use and death among patients with chronic obstructive pulmonary disease (COPD) has been tested. Using Mississippi Medicaid data, we examined the association of transient or short-term opioid use and acute respiratory exacerbations among adults with COPD. We used a case-crossover design and 2013–2017 Mississippi Medicaid administrative claims data. A total of 1,972 qualifying exacerbation events occurred in 1,354 beneficiaries. The frequency and dose of opioid exposure in the 7 days before the exacerbation were examined and compared with the opioid exposure in 10 control windows, each 7 days long, before the exacerbation. Adjusted odds ratios were estimated using conditional logistic regression models to estimate the risk of opioid use on exacerbations after accounting for use of bronchodilators, corticosteroids, benzodiazepines, and β-blockers. Overall, opioid exposure in the 7 days before an exacerbation was significantly associated with acute respiratory exacerbation (odds ratio = 1.81; 95% confidence interval: 1.60, 2.05). Each 25-mg increase in morphine equivalent daily dose was associated with an 11.2% increase in the odds of an acute respiratory exacerbation (odds ratio = 1.11; 95% confidence interval: 1.04, 1.20). Transient use of opioids was significantly associated with acute respiratory exacerbation of COPD.
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Bourbeau, Jean, and Carlos Echevarria. "Models of care across the continuum of exacerbations for patients with chronic obstructive pulmonary disease." Chronic Respiratory Disease 17 (January 1, 2020): 147997311989545. http://dx.doi.org/10.1177/1479973119895457.
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Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with significant morbidity and mortality, and treatments require a multidisciplinary approach to address patient needs. This review considers different models of care across the continuum of exacerbations (1) chronic care and self-management interventions with the action plan, (2) domiciliary care for severe exacerbation and the impact on readmission prevention and (3) the discharge care bundle for management beyond the acute exacerbation episode. Self-management strategies include written action plans and coaching with patient and family support. Self-management interventions facilitate the delivery of good care, can reduce exacerbations associated with admission, be cost-effective and improve quality of life. Hospitalization as a complication of exacerbation is not always unavoidable. Domiciliary care has been proposed as a solution to replace part, and perhaps even all, of the patient’s in-hospital stay, and to reduce hospital bed days, readmission rates and costs; low-risk patients can be identified using risk stratification tools. A COPD discharge bundle is another potentially important approach that can be considered to improve the management of COPD exacerbations complicated by hospital admission; it comprised treatments that have demonstrated efficacy, such as smoking cessation, personalized pharmacotherapy and non-pharmacotherapy such as pulmonary rehabilitation. COPD bundles may also improve the transition of care from the hospital to the community following exacerbation and may reduce readmission rates. Future models of care should be personalized – providing patient education aiming at behaviour changes, identifying and treating co-morbidities, and including outcomes that measure quality of care rather than focusing only on readmission quantity within 30 days.
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Wang, Kay, Jan Y. Verbakel, Jason Oke, Alexander Fleming-Nouri, Josh Brewin, Nia Roberts, Norihiro Harada, et al. "Using fractional exhaled nitric oxide to guide step-down treatment decisions in patients with asthma: a systematic review and individual patient data meta-analysis." European Respiratory Journal 55, no. 5 (March 5, 2020): 1902150. http://dx.doi.org/10.1183/13993003.02150-2019.
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BackgroundHigh exhaled nitric oxide fraction (FENO) levels are associated with greater risk of asthma exacerbation. However, it is not clear how FENO can be used to guide safe reductions in inhaled corticosteroid (ICS) doses in asthma patients. This study assesses the ability of FENO to guide ICS reductions.MethodsSystematic searching of electronic databases identified prospective observational studies and randomised controlled trials which recruited participants with mild-to-moderate asthma aged ≥12 years and measured FENO before reducing ICS. We performed multilevel mixed-effects logistic regression in relation to acute exacerbations and estimated each participant's exacerbation risk using our logistic regression model.ResultsWe included data from seven out of eight eligible studies, representing 384 participants. ICS doses were halved in four studies and withdrawn in three studies. A baseline FENO measurement of ≥50 ppb was associated with increased risk of exacerbations (crude OR 3.14, 95% CI 1.41–7.00, p=0.005; adjusted OR 3.08, 95% CI 1.36–6.98, p=0.007) and corresponded to an estimated exacerbation risk cut-off of 15%. Reducing ICS when estimated exacerbation risk was <15% versus <10% would result in fewer patients remaining on the same ICS dose (40 (10.4%) out of 384 versus 141 (36.7%) out of 384), but similar proportions of patients avoiding exacerbations (222 (91.4%) out of 243, 95% CI 87.1–94.6% versus 311 (90.4%) out of 344, 95% CI 86.8–93.3%).ConclusionIn patients with mild-to-moderate asthma, gradual ICS reduction when FENO is <50 ppb may help decrease ICS use without increasing exacerbations. Future research should aim to validate these findings in larger populations.
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Zheshko, O. M., O. D. Shulga, M. I. Dubinets, O. A. Yurko, and O. R. Lopachak. "EXACERBATION OF MULTIPLE SCLEROSIS: A CLINICAL PARACLINICAL PARADOX." PRECARPATHIAN BULLETIN OF THE SHEVCHENKO SCIENTIFIC SOCIETY Pulse, no. 5(57) (April 24, 2019): 65–69. http://dx.doi.org/10.21802/2304-7437-2019-5(57)-65-69.
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The purpose of our work was to find out the factors that determine the treatment tactics in the presence of signs of clinical and / or radiological exacerbation in patients with remitting multiple sclerosis. 104 patients were examined, 36.25 ± 9.81 years old. It has been established that in patients with shorter duration of the disease, the incidence of clinical (p <0.001) and radiological exacerbations (p <0.001) is higher. In patients who do not receive immunomodulatory therapy (p <0.05), there are signs of both clinical and radiological exacerbation. Patients with clinical exacerbations, regardless of the presence of active foci, receive treatment with methylprednisolone in almost 95% of cases. At the same time, in the case of radiological exacerbation, treatment with methylprednisolone is prescribed in only one third of the cases.
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Zheshko, O. M., O. D. Shulga, M. I. Dubinets, O. A. Yurko, and O. R. Lopachak. "EXACERBATION OF MULTIPLE SCLEROSIS: A CLINICAL PARACLINICAL PARADOX." PRECARPATHIAN BULLETIN OF THE SHEVCHENKO SCIENTIFIC SOCIETY Pulse, no. 5(57) (April 24, 2019): 65–69. http://dx.doi.org/10.21802/10.21802/2304-7437-2019-5(57)-65-69.
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The purpose of our work was to find out the factors that determine the treatment tactics in the presence of signs of clinical and / or radiological exacerbation in patients with remitting multiple sclerosis. 104 patients were examined, 36.25 ± 9.81 years old. It has been established that in patients with shorter duration of the disease, the incidence of clinical (p <0.001) and radiological exacerbations (p <0.001) is higher. In patients who do not receive immunomodulatory therapy (p <0.05), there are signs of both clinical and radiological exacerbation. Patients with clinical exacerbations, regardless of the presence of active foci, receive treatment with methylprednisolone in almost 95% of cases. At the same time, in the case of radiological exacerbation, treatment with methylprednisolone is prescribed in only one third of the cases.
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Arkhipov, V. V. "Prevention of copd exacerbations. Focus on dual bronchodilators." Medical Council, no. 15 (October 12, 2018): 8–17. http://dx.doi.org/10.21518/2079-701x-2018-15-8-17.
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COPD exacerbations occur in almost all patients, and half of patients in the Russian Federation (52%) have two or more exacerbations per year or require urgent admission to hospital. COPD exacerbations come from increased acute inflammation in the respiratory tract of a patient under the influence of many factors. Modern pharmacotherapy provides the physician with several options in reducing the number of exacerbations. This review provides evidence about the maximum reduction in exacerbation risk due to the administration of tiotropium/olodaterol combination or triple therapy.
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Jacob, Ariane, Catherine Laurin, Kim L. Lavoie, Gregory Moullec, Maxine Boudreau, Catherine Lemière, and Simon L. Bacon. "The Impact Of Body Mass Index On Inpatient- Versus Outpatient-Treated Chronic Obstructive Pulmonary Disease Exacerbations." Canadian Respiratory Journal 20, no. 4 (2013): 237–42. http://dx.doi.org/10.1155/2013/131072.
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BACKGROUND: Increased body weight has been associated with worse prognoses for many chronic diseases; however, this relationship is less clear in patients with chronic obstructive pulmonary disease (COPD), with underweight patients experiencing higher morbidity than normal or overweight patients.OBJECTIVE: To assess the impact of body mass index (BMI) on the risk for COPD exacerbations.METHODS: The present study included 115 patients with stable COPD (53% women; mean [± SD] age 67±8 years). Height and weight were measured to calculate BMI. Patients were followed for a mean of 1.8±0.8 years to assess the prospective risk of inpatient-treated exacerbations and outpatient-treated exacerbations, all of which were verified by chart review.RESULTS: Cox regression models revealed that underweight patients were at greater risk for inhospital-treated exacerbations (RR 2.93 [95% CI 1.27 to 6.76) relative to normal weight patients. However, overweight (RR 0.59 [95% CI 0.33 to 1.57) and obese (RR 0.99 [95% CI 0.53 to 1.86]) patients did not differ from normal weight patients. All analyses were adjusted for age, sex, length of diagnosis, smoking pack-years, forced expiratory volume in 1 s, and time between recruitment and last exacerbation. BMI did not influence the risk of out-of-hospital exacerbations.CONCLUSIONS: The present study showed that underweight patients were at greater risk for inhospital exacerbations. However, BMI did not appear to be a risk factor for out-of-hospital exacerbations. This suggests that the BMI-exacerbation link may differ according to the nature of the exacerbation, the mechanisms for which are not yet known.
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Avdeev, S. N., A. S. Belevskiy, Z. R. Aisanov, V. V. Arkhipov, I. V. Leshchenko, S. I. Ovcharenko, A. I. Sinopal’nikov, et al. "Possibilities to prevent acute exacerbation of chronic obstructive pulmonary disease using inhalational therapy. A Report of Expert Panel of Russian Respiratory Society." Russian Pulmonology 28, no. 3 (July 30, 2018): 368–80. http://dx.doi.org/10.18093/0869-0189-2018-28-3-368-380.
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An impact of acute exacerbation of COPD (AECOPD) on the course and the prognosis of chronic obstructive pulmonary disease depends on severity of the exacerbation. Moderate and severe exacerbations are considered as clinically significant events. Clinical studies investigating a role of inhalational therapy for the risk of AECOPD differed significantly in important parameters and the patients involved were not fully described in the real clinical practice. Tiotropium alone did not demonstrate any benefit over other inhalational therapies, such as inhaled corticosteroid/long-acting β2-agonist (ICS/LABA) combinations and long-acting muscarinic antagonist (LAMA)/LABA combinations, for risk reduction of moderate to severe exacerbations. A benefit of tiotropium/olodaterol combination over tiotropium for the reduction of risk of clinically significant exacerbations was first shown in DYNAGITO study; patients’ groups in this study did not differ in a rate and a spectrum of adverse events including cardiovascular events. An efficient bronchodilating therapy should be administered to all patients with COPD as it could improve dyspnea and prevent exacerbations. Further escalation of treatment in patients with frequent exacerbations of COPD should be personalized according to clinical course and causes of AECOPD.
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Csoma, Balázs, András Bikov, Ferenc Tóth, György Losonczy, Veronika Müller, and Zsófia Lázár. "Blood eosinophils on hospital admission for COPD exacerbation do not predict the recurrence of moderate and severe relapses." ERJ Open Research 7, no. 1 (January 2021): 00543–2020. http://dx.doi.org/10.1183/23120541.00543-2020.
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Background and objectiveThe relationship between hospitalisation with an eosinophilic acute exacerbation of COPD (AE-COPD) and future relapses is unclear. We aimed to explore this association by following 152 patients for 12 months after hospital discharge or until their first moderate or severe flare-up.MethodsPatients hospitalised with AE-COPD were divided into eosinophilic and non-eosinophilic groups based on full blood count results on admission. All patients were treated with a course of systemic corticosteroid. The Cox proportional hazards model was used to study the association with the time to first re-exacerbation; a generalised linear regression model was applied to identify clinical variables related to the recurrence of relapses.ResultsWe did not find a difference in the time to the next moderate or severe exacerbation between the eosinophilic (≥2% of total leukocytes and/or ≥200 eosinophils·µL−1, n=51, median (interquartile range): 21 (10–36) weeks) and non-eosinophilic groups (n=101, 17 (9–36) weeks, log-rank test: p=0.63). No association was found when other cut-off values (≥3% of total leukocytes and/or ≥300 eosinophils·µL−1) were used for the eosinophilic phenotype. However, the higher number of past severe exacerbations, a lower forced expiratory volume in 1 s (FEV1) at discharge and higher pack-years were related to shorter exacerbation-free time. According to a subgroup analysis (n=73), 48.1% of patients with initial eosinophilic exacerbations had non-eosinophilic relapses on readmission.ConclusionsOur data do not support an increased risk of earlier recurring moderate or severe relapses in patients hospitalised with eosinophilic exacerbations of COPD. Eosinophilic severe exacerbations present a variable phenotype.
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Kerkhof, Marjan, Isha Chaudhry, Ian D. Pavord, Marc Miravitlles, Chin Kook Rhee, David M. G. Halpin, Omar S. Usmani, et al. "Blood eosinophil count predicts treatment failure and hospital readmission for COPD." ERJ Open Research 6, no. 4 (October 2020): 00188–2020. http://dx.doi.org/10.1183/23120541.00188-2020.
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We examined associations between blood eosinophil counts (BEC) and risk of treatment failure or hospital readmission following acute oral corticosteroid (OCS)-treated COPD exacerbations.We conducted studies from the Optimum Patient Care Research Database (OPCRD) (www.optimumpatientcare.org/opcrd) and Clinical Practice Research Datalink (CPRD) (www.cprd.com/home/), validated databases for medical research, with linked Hospital Episode Statistics (HES) data for ∼20 000 COPD patients aged ≥40 years. For patients with OCS-treated COPD exacerbations treated in primary care, with BECs recorded on first day of OCS treatment (Cohort 1), we assessed treatment failure (COPD-related hospitalisations and OCS prescriptions beyond index OCS course). For patients hospitalised for COPD exacerbations, with BEC measured over an exacerbation-free period during the year prior to admission (Cohort 2), we assessed readmission rate. Cox proportional hazards regression analysis was adjusted for confounders to estimate the association between BEC and treatment outcomes.Of patients treated with OCS for COPD exacerbations in primary care (Cohort 1), 44% experienced treatment failure following single OCS courses, and 10% (255/2482) were hospitalised for ≤6 weeks. Greater BEC was associated with reduced hospital-admission risk (hazard ratio [HR]=0.26; 95% CI: 0.12–0.56, per 100 cells·µL−1 increase). BEC increases of ≥200 cells·µL−1 from exacerbation-free periods to exacerbations were associated with least hospitalisation risk (HR=0.32; 95% CI: 0.15–0.71) versus no BEC change. For patients hospitalised for COPD exacerbations (Cohort 2), 4-week hospital readmission was 12% (1189/10 245). BEC increases during an exacerbation-free period within the past year were associated with reduced risk of short-term readmission (HR=0.78; 95% CI: 0.63–0.96).Greater BEC predicted better outcomes for patients with OCS-treated COPD exacerbations, whether community or hospital managed. Eosinopenia predicted worse outcomes.
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Bidder, Therese M., and Douglas S. Robinson. "Asthma Exacerbations – The Focus For Treatment Of Severe Asthma?" European Respiratory & Pulmonary Diseases 01, no. 01 (2015): 18. http://dx.doi.org/10.17925/erpd.2015.01.01.18.
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Asthma exacerbations (worsening of symptoms requiring oral corticosteroid treatment) impair quality of life, interfere with normal activities and can lead to hospital admission or even death. Predicting and preventing exacerbations is therefore an important focus in asthma management. Good patient education and adherence with appropriate treatment are important, as is detection of when this is not achieved. Increasingly it is recognised that uncontrolled airway inflammation in a risk factor for exacerbation, and detection and control of untreated inflammation can reduce exacerbation rates. As specific biologics are available for asthma treatment it will be important to use biomarkers to select those subgroups that will benefit from each type of treatment.
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Ortega, Hector, Beth Hahn, Michael Bogart, Christopher F. Bell, Tim Bancroft, Benjamin Chastek, and Jean-Pierre Llanos. "Impact of mepolizumab on exacerbations in severe asthma: Results from a U.S. insurance claims data base." Allergy and Asthma Proceedings 41, no. 5 (September 1, 2020): 341–47. http://dx.doi.org/10.2500/aap.2020.41.200043.
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Background: In controlled clinical studies, mepolizumab has been shown to reduce exacerbation rates and the use of oral corticosteroids as well as improve asthma control and health-related quality of life compared with placebo in patients with severe eosinophilic asthma. However, real-world data on the impact of mepolizumab on clinical outcomes are limited. Objective: To evaluate the effect of mepolizumab on asthma exacerbations and asthma exacerbation‐related costs in patients with severe asthma in U.S. clinical practice. Methods: This retrospective cohort study used U.S. administrative claims data from patients ages ≥12 years and with severe asthma at mepolizumab treatment initiation (index date; identification period, January 2015‐June 2017) who had received two or more mepolizumab administrations within 180 days of the index date and had no evidence of treatment with another asthma biologic. The exacerbation rate and exacerbation-related costs were assessed in both the 12 months before mepolizumab initiation (baseline period) and the following 12 months (follow-up period). A clinical trial‐like cohort was identified, defined as patients with two or more baseline exacerbations and ≥10 administrations during follow-up. Results: A total of 201 patients were included in the overall population and 74 patients in the clinical trial‐like cohort. Mepolizumab significantly reduced the exacerbation rate between the baseline and follow-up periods in both the overall population and the clinical trial‐like cohort (p < 0.001), which corresponded to 33.6% and 48.6% reductions, respectively. The rate of exacerbations in patients who required hospitalization between the baseline and follow-up periods was also reduced by 35.3% (p = 0.080) and 68.2% (p = 0.015) in the overall population and in the clinical trial‐like cohort, respectively. Cost data were inconclusive. Conclusion: This study, which used real-world data, demonstrated that mepolizumab is associated with reductions in asthma exacerbations, in line with the findings from controlled clinical studies. These results provided further evidence of the effectiveness of mepolizumab in a real-world setting.
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Avdeev, S. N., V. V. Gaynitdinova, Z. M. Merzhoeva, G. V. Neklyudova, N. A. Tsareva, and G. S. Nuralieva. "Exacerbation of idiopathic pulmonary fibrosis." Terapevticheskii arkhiv 92, no. 3 (April 27, 2020): 73–77. http://dx.doi.org/10.26442/00403660.2020.03.000402.
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Idiopathic pulmonary fibrosis (IPF) is usually characterized by a chronic and slowly progressive course. According to several studies, a small number of patients with IPF (about 515%) develops an acute deterioration of deasese exacerbation of IPF. Exacerbations of IPF can occur at any time of the disease and sometimes becomes the first manifestation of IPF. Pulmonary hypertension in IPF is a fairly frequent complication, which leads to severe violations of gas exchange and reduced tolerance to physical stress. Currently, proven effective treatments for exacerbations of IPF do not exist, the management of this condition is based on supportive therapy (oxygen, respiratory support) and interventions with inadequate evidences (corticosteroids, immunosuppressant). During exacerbation of IPF a careful search of all the possible triggers is justified. In the presented clinical case of exacerbation of IPF there was demonstrated the efficacy of complex therapy including antifibrotic therapy, PAH-specific medicines and enhanced oxygen therapy.
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Singanayagam, Aran, Su-Ling Loo, Maria Calderazzo, Lydia J. Finney, Maria-Belen Trujillo Torralbo, Eteri Bakhsoliani, Jason Girkin, et al. "Antiviral immunity is impaired in COPD patients with frequent exacerbations." American Journal of Physiology-Lung Cellular and Molecular Physiology 317, no. 6 (December 1, 2019): L893—L903. http://dx.doi.org/10.1152/ajplung.00253.2019.
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Patients with frequent exacerbations represent a chronic obstructive pulmonary disease (COPD) subgroup requiring better treatment options. The aim of this study was to determine the innate immune mechanisms that underlie susceptibility to frequent exacerbations in COPD. We measured sputum expression of immune mediators and bacterial loads in samples from patients with COPD at stable state and during virus-associated exacerbations. In vitro immune responses to rhinovirus infection in differentiated primary bronchial epithelial cells (BECs) sampled from patients with COPD were additionally evaluated. Patients were stratified as frequent exacerbators (≥2 exacerbations in the preceding year) or infrequent exacerbators (<2 exacerbations in the preceding year) with comparisons made between these groups. Frequent exacerbators had reduced sputum cell mRNA expression of the antiviral immune mediators type I and III interferons and reduced interferon-stimulated gene (ISG) expression when clinically stable and during virus-associated exacerbation. A role for epithelial cell-intrinsic innate immune dysregulation was identified: induction of interferons and ISGs during in vitro rhinovirus (RV) infection was also impaired in differentiated BECs from frequent exacerbators. Frequent exacerbators additionally had increased sputum bacterial loads at 2 wk following virus-associated exacerbation onset. These data implicate deficient airway innate immunity involving epithelial cells in the increased propensity to exacerbations observed in some patients with COPD. Therapeutic approaches to boost innate antimicrobial immunity in the lung could be a viable strategy for prevention and treatment of frequent exacerbations.
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Tanimura, Kazuya, Susumu Sato, Atsuyasu Sato, Naoya Tanabe, Koichi Hasegawa, Kiyoshi Uemasu, Yoko Hamakawa, Toyohiro Hirai, and Shigeo Muro. "Low serum free light chain is associated with risk of COPD exacerbation." ERJ Open Research 6, no. 2 (April 2020): 00288–2019. http://dx.doi.org/10.1183/23120541.00288-2019.
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BackgroundMost exacerbations of chronic obstructive pulmonary disease (COPD) are triggered by respiratory tract infections. Adaptive immunity via antibody production is important in preventing infections. Impaired antibody production is reported to be associated with an increased risk of exacerbations of COPD. In the present study, we elucidated whether reduced free light chains (FLCs), which are excessive amounts of light chains produced during antibody synthesis and can be used to estimate systemic antibody production, may be a promising biomarker to predict the risk of exacerbations of COPD.MethodsWe enrolled stable male patients with COPD and prospectively observed them for 2 years. At baseline, serum combined FLC (cFLC; sum of kappa and lambda values) and pulmonary function were evaluated. Exacerbation was defined as a worsening of symptoms requiring treatments with antibiotics, corticosteroids or both.Results63 patients with stable COPD were enrolled (72.8±8.1 years, GOLD A/B/C/D=24/28/6/5), and 51 patients completed the 2-year follow-up. Serum cFLC was 31.1 mg·L−1 on average and ranged widely (1.4 to 89.9 mg·L−1). The patients with low cFLC (below the mean−sd, n=6) experienced a significantly shorter time to the first exacerbation of COPD (p<0.0001 by the log-rank test). A multivariate Cox proportional hazard model, including the COPD assessment test score, % predicted forced expiratory volume in 1 s (FEV1 % pred), and number of previous exacerbations demonstrated that low cFLC and low FEV1 % pred were independently and significantly correlated with the risk for exacerbations of COPD.ConclusionLow cFLC may be a B-cell-associated novel biomarker associated with risk of COPD exacerbation.
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Kim, Victor, and Shawn D. Aaron. "What is a COPD exacerbation? Current definitions, pitfalls, challenges and opportunities for improvement." European Respiratory Journal 52, no. 5 (September 20, 2018): 1801261. http://dx.doi.org/10.1183/13993003.01261-2018.
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Chronic obstructive pulmonary disease (COPD) is a chronic illness that can be periodically punctuated by exacerbations, characterised by acute worsening of symptoms, including increased dyspnoea, cough, sputum production and sputum purulence. COPD exacerbations are common and have important clinical and economic consequences, including lost work productivity, increased utilisation of healthcare resources, temporary or permanent reductions in lung function and exercise capacity, hospitalisation, and sometimes death. Over the past two decades, clinicians and researchers have broadened their treatment goals for COPD to extend beyond improving lung function and symptoms, and have begun to address the importance of preventing and reducing exacerbations. However, despite the best efforts of clinicians and guideline committees, current definitions of COPD exacerbations are imperfect and fraught with problems. The cardinal symptoms of a COPD exacerbation are nonspecific and can result from acute cardiorespiratory illnesses other than COPD. A proposed definition, which may be more specific than current definitions, suggests that COPD exacerbation be defined as an acute or subacute worsening of dyspnoea (≥5 on a visual analogue scale that ranges from 0 to 10) sometimes but not necessarily accompanied by increased cough, sputum volume and/or sputum purulence. Necessary laboratory criteria for an exacerbation include oxygen desaturation ≤4% below that of stable state, elevated levels of circulating blood neutrophils or eosinophils (≥9000 neutrophils·mm−3 or ≥2% blood eosinophils) and elevated C-reactive protein (≥3 mg·L−1), without evidence of pneumonia or pulmonary oedema on chest radiography and with negative laboratory test results for other aetiologies. Herein, we discuss the current state of the art with respect to how we define COPD exacerbations, associated pitfalls and challenges, and opportunities for improvement.
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Sakae, Thiago Mamoru, Marcia Margaret Menezes Pizzichini, Paulo Jose Zimermann Teixeira, Rosemeri Maurici da Silva, Daisson Jose Trevisol, and Emilio Pizzichini. "Exacerbations of COPD and symptoms of gastroesophageal reflux: a systematic review and meta-analysis." Jornal Brasileiro de Pneumologia 39, no. 3 (June 2013): 259–71. http://dx.doi.org/10.1590/s1806-37132013000300002.
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OBJECTIVE: To examine the relationship between gastroesophageal reflux (GER) and COPD exacerbations. METHODS: We conducted a systematic search of various electronic databases for articles published up through December of 2012. Studies considered eligible for inclusion were those dealing with COPD, COPD exacerbations, and GER; comparing at least two groups (COPD vs. controls or GER vs. controls); and describing relative risks (RRs) and prevalence ratios-or ORs and their respective 95% CIs (or presenting enough data to allow further calculations) for the association between GER and COPD-as well as exacerbation rates. Using a standardized form, we extracted data related to the study design; criteria for GER diagnosis; age, gender, and number of participants; randomization method; severity scores; methods of evaluating GER symptoms; criteria for defining exacerbations; exacerbation rates (hospitalizations, ER visits, unscheduled clinic visits, prednisone use, and antibiotic use); GER symptoms in COPD group vs. controls; mean number of COPD exacerbations (with symptoms vs. without symptoms); annual frequency of exacerbations; GER treatment; and severity of airflow obstruction. RESULTS: Overall, GER was clearly identified as a risk factor for COPD exacerbations (RR = 7.57; 95% CI: 3.84-14.94), with an increased mean number of exacerbations per year (mean difference: 0.79; 95% CI: 0.22-1.36). The prevalence of GER was significantly higher in patients with COPD than in those without (RR = 13.06; 95% CI: 3.64-46.87; p < 0.001). CONCLUSIONS: GER is a risk factor for COPD exacerbations. The role of GER in COPD management should be studied in greater detail.
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Kirenga, Bruce J., Corina de Jong, Levicatus Mugenyi, Winceslaus Katagira, Abdallah Muhofa, Moses R. Kamya, H. Marike Boezen, and Thys van der Molen. "Rates of asthma exacerbations and mortality and associated factors in Uganda: a 2-year prospective cohort study." Thorax 73, no. 10 (May 11, 2018): 983–85. http://dx.doi.org/10.1136/thoraxjnl-2017-211157.
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Data on asthma treatment outcomes in Africa are limited. 449 patients with asthma (age 5–93 years) in Uganda were followed up for 2 years to determine rates of exacerbations and mortality and associated factors. During follow-up the median number of exacerbations per patient was 1 (IQR 0–5) and 17 patients died (3.7%, 27.3 deaths per 1000 person years). Considering only the first year of follow-up, 59.6% of the patients experienced at least one exacerbation, 32.4% experienced three or more exacerbations. A multivariable model showed that the likelihood of experiencing at least one exacerbation in the first year of follow-up was lower with better baseline asthma control (higher asthma control test (ACT) score), with OR 0.87 (95% CI: 0.82 to 0.93, P=0.000), and was higher with more exacerbations in the year prior to enrolment (OR for log number of exacerbations 1.28, 95% CI: 1.04 to 1.57, P=0.018). Better asthma control (OR 0.93, 95% CI: 0.88 to 0.99, P=0.021) and number of baseline exacerbations (OR 1.35,95% CI: 1.11 to 1.66, P=0.005) were also the only factors that were independently associated with experiencing three or more exacerbations during the first year of follow-up. The only factor found to be associated with all-cause mortality was FEV1, with higher recent FEV1 associated with lower all-cause mortality (OR 0.30, 95% CI: 0.14 to 0.65; P=0.002). Rates of asthma exacerbations and mortality are high in Uganda and are associated with poor asthma control. Health systems should be strengthened to care for asthma patients.
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Shah, Syed A., Jennifer K. Quint, Bright I. Nwaru, and Aziz Sheikh. "Impact of COVID-19 national lockdown on asthma exacerbations: interrupted time-series analysis of English primary care data." Thorax 76, no. 9 (March 29, 2021): 860–66. http://dx.doi.org/10.1136/thoraxjnl-2020-216512.
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BackgroundThe impact of COVID-19 and ensuing national lockdown on asthma exacerbations is unclear.MethodsWe conducted an interrupted time-series (lockdown on 23 March 2020 as point of interruption) analysis in asthma cohort identified using a validated algorithm from a national-level primary care database, the Optimum Patient Care Database. We derived asthma exacerbation rates for every week and compared exacerbation rates in the period: January to August 2020 with a pre-COVID-19 period and January to August 2016–2019. Exacerbations were defined as asthma-related hospital attendance/admission (including accident and emergency visit), or an acute course of oral corticosteroids with evidence of respiratory review, as recorded in primary care. We used a generalised least squares modelling approach and stratified the analyses by age, sex, English region and healthcare setting.ResultsFrom a database of 9 949 387 patients, there were 100 165 patients with asthma who experienced at least one exacerbation during 2016–2020. Of 278 996 exacerbation episodes, 49 938 (17.9%) required hospital visit. Comparing pre-lockdown to post-lockdown period, we observed a statistically significant reduction in the level (−0.196 episodes per person-year; p<0.001; almost 20 episodes for every 100 patients with asthma per year) of exacerbation rates across all patients. The reductions in level in stratified analyses were: 0.005–0.244 (healthcare setting, only those without hospital attendance/admission were significant), 0.210–0.277 (sex), 0.159–0.367 (age), 0.068–0.590 (region).ConclusionsThere has been a significant reduction in attendance to primary care for asthma exacerbations during the pandemic. This reduction was observed in all age groups, both sexes and across most regions in England.