Journal articles on the topic 'Airway obstruction. Compression of lung tissue'

Frequency-dependent characteristics of lung resistance (Rl) and elastance (El) are sensitive to different patterns of airway obstruction. We used an enhanced ventilator waveform (EVW) to measure inspiratory Rl and El spectra in ventilated patients during thoracic surgery. The EVW delivers an inspiratory flow waveform with enhanced spectral excitation from 0.156 to 8.1 Hz. Estimates of the coefficients in a trigonometric approximation of the EVW flow and transpulmonary pressure inspirations yielded inspiratory Rl and Elspectra. We applied the EVW in a group with mild obstruction undergoing various thoracoscopic procedures ( n = 6), and another group with severe chronic obstructive pulmonary disease undergoing lung volume reduction surgery ( n = 8). Measurements were made at positive end-expiratory pressure (PEEP) of 0, 3, and 6 cmH2O. Inspiratory Rl was similar in both groups despite marked differences in spirometry. The chronic obstructive pulmonary disease patients demonstrated a pronounced frequency-dependent increase in inspiratory El consistent with severe heterogeneous peripheral airway obstruction. PEEP appears to have beneficial effects by reducing peripheral airway resistance. Lung volume reduction surgery resulted in increased inspiratory Rl and El at all frequencies and PEEPs, possibly due to loss of diseased lung tissue, pulmonary edema, increased mechanical heterogeneity, and/or an improvement in airway tethering.

AbstractThe lung is an inherently mechanosensitive organ, where cells of the airway and parenchyma experience a range of mechanical forces throughout life including shear, stretch, and compression, in both health and disease. In this regard, pediatric and adult lung diseases such as wheezing and asthma, bronchopulmonary dysplasia (BPD), chronic obstructive pulmonary disease (COPD), and pulmonary fibrosis (PF) all involve macroscopic and cellular changes to the mechanical properties of the bronchial airways and/or parenchyma to varying extents. Accordingly, understanding how mechanical forces are sensed in the lung, and the responses of cells and tissues in the context of normal development and health versus disease conditions becomes highly relevant. There is increasing recognition that transduction of mechanical forces into cellular responses involves a number of channels, some of which are inherently mechanosensitive. Such channels trigger mechanotransduction pathways that may further mediate cellular remodeling, inflammation, and other pathophysiologic mechanisms in response to stretch, stiffness, and inflammatory cascades. Two particularly important channel families have emerged in pulmonary pathophysiology: the transient receptor potential vanilloid family with focus on member TRPV4 and the recently identified Piezo (PZ) channels. Here, we explore current understanding of the contributions of TRPV4 and PZ channels in lung health and disease states, focusing on the interactions between these mechanosensitive channels and their local environment including immune cells, the extracellular matrix, and cellular cytoskeletal elements. We further discuss potential areas for future research to better understand the impact of mechanical channels on pulmonary health and disease. © 2023 American Physiological Society. Compr Physiol 13:5157‐5178, 2023.

Introduction. Aberrations in pulmonary function test are present in about 20% of patients with radiographic stage I sarcoidosis, whereas the pulmonary function is damaged in 40-80% of patients with parenchymal infiltrates (stages II, III or IV). Discussion and Review of Literature. Reductions in lung volumes (vital capacity and total lung capacity) are characteristic. The diffusing capacity of lungs is often reduced, but it is less pronounced in sarcoidosis than in idiopathic pulmonary fibrosis. Oxygenation is usually preserved until late in the course of sarcoidosis. Airflow obstruction (reduced forced expiratory volume in one second and expiratory flow rates) and bronchial hyper-reactivity occur in 30-50% of sarcoidosis patients with pulmonary parenchymal involvement. Conclusion. While restrictive spirometry pattern could easily be explained by fibrous changes in lung parenchyma, especially in late stages of the lung disease, pathogenesis of airflow limitation can be attributed mostly to endobronchial involvement (intraluminal granuloma or fibrous scars formation), airway compression due to enlarged lymph nodes and to distortion of small airways due to established pulmonary fibrosis.

Tumors of the thyroid gland, due to their localization in the neck, can as they grow pose a threat to the airway. Thyroid malignancies, aside from compression, can also infiltrate local tissue. The case presented is that of a female patient with advanced thyroid cancer that required urgent airway management, but due to the propagation of the malignancy into the mediastinum and consequent compression of distal trachea and lung tissue, the hospitalization ended with a fatal outcome regardless of the treatment undertaken. Even advanced airway management methods (endotracheal intubation or tracheotomy) are sometimes not enough to save our patients' lives.

Horses are prone to recurrent airway obstruction (RAO), an inflammatory lung disease induced by repeated exposure to environmental mold, dust, and bacterial components. Active disease manifests with mucus hyperproduction, neutrophilic inflammation, bronchoconstriction, and coughing. Chronically affected animals have lung remodeling characterized by smooth muscle hyperplasia, collagen deposition, lymphoid hyperplasia, and impaired aerobic performance. Clara cell secretory protein (CCSP) counters inflammation in the lung, hence we hypothesized that CCSP depletion is a key feature of RAO in horses. Recombinant equine CCSP and specific antiserum were produced, and percutaneous lung biopsies were obtained from 3 healthy horses and from 3 RAO-affected horses before and after induction of RAO. CCSP relative gene expression in tissue, as well as protein concentration in lung lavage fluid, was determined. Immunocytochemical analysis, using both light and immunogold ultrastructural methods, demonstrated reduced CCSP staining in lung tissue of animals with RAO. Immunogold label in Clara cell granules was less in animals with chronic RAO than in normal animals, and absent in animals that had active disease. Median lung lavage CCSP concentration was 132 and 129 ng/ml in healthy horses, and 62 and 24 ng/ml in RAO horses before and after challenge, respectively. CCSP lung gene expression was significantly higher in healthy animals than in animals with chronic RAO. Together, these preliminary findings suggest that reduced production of CCSP and subcellular changes in Clara cells are features of chronic environmentally induced lung inflammation in horses.

We reasoned that if flow limitation plays an important role in lung hyperinflation, then bronchodilatation should be associated with a decrease of functional residual capacity (FRC) only in subjects breathing under conditions of flow limitation. This hypothesis was tested in 33 subjects with chronic airway narrowing due to asthma or chronic obstructive pulmonary disease (COPD). Flow limitation during tidal breathing was inferred from the impingement of the tidal flow-volume loop on the flow recorded during submaximally forced expiratory manoeuvres initiated from end-tidal inspiration. At baseline, flow limitation during tidal breathing was present in seven asthmatic (Group 1) and eight COPD subjects (Group 2), but absent in 11 asthmatic (Group 3) and seven COPD subjects (Group 4). FRC (mean+/-SEM) was similar in the four groups (range 117+/-7 to 134+/-6% of predicted). Inhalation of salbutamol (200 microg) caused significant increments of the forced expiratory volume in one second (FEVI) (range 6+/-1 to 21+/-8% of baseline) and forced expiratory flows at 30% of baseline forced vital capacity (V'30) (range 58+/-13 to 235+/-93% of baseline) in all groups. In groups with flow limitation during tidal breathing at baseline the FRC measured by plethysmography decreased significantly (12+/-2% in Group 1, and 9+/-2% in Group 2), and the inspiratory capacity (IC) measured by spirometry increased significantly (17+/-3% in Group 1 and 7+/-3% in Group 2). This was associated with flow limitation disappearing at the volume of baseline end-tidal expiration. In Groups 3 and 4 neither FRC nor IC changed significantly. The breathing pattern was not modified in any group after salbutamol. These findings suggest that flow limitation may contribute to generation of lung hyperinflation both in asthma and chronic obstructive pulmonary disease. We speculate that the increment of functional residual capacity could be triggered by dynamic airway compression downstream from the flow-limiting segment.

Abstract Our research objective is to examine the role of dysregulated immune responses in disease progression and changes in lung physiology in a rat model of COPD. Spontaneously hypertensive rats were exposed to tobacco smoke (TS) (90 mg/m3) or filtered air (FA) for up to 12 weeks. Necropsy timepoints of 4, 6, 8, 10 and 12 weeks were chosen to define the immunological and pathophysiological changes in the lung. Rats exposed to TS showed significant increases in macrophage, neutrophil and lymphocyte number in bronchoalveolar lavage compared to FA at all weeks examined. Proinflammatory cytokines IL-1β, IL-6 and IFN-γ in whole lung homogenates were significantly increased following exposure to TS compared to FA controls. Physiological airway obstruction due to TS exposure was noted by significant elevations in central airway resistance and tissue damping. Central airway resistance was significantly increased at 4 weeks, decreased at 6 weeks, but returned to significantly elevated levels at 10 and 12 weeks following TS exposure. Tissue damping showed a peak at 4 weeks, then a decreasing trend, although remaining significantly elevated through 12 weeks of TS exposure. Strong positive correlations were noted between proinflammatory cytokines IL-1β, IL-6, IFN-γ, TNF-α and the degree of tissue damping. These changes were associated with increases in central airway squamous epithelial metaplasia and distal airway mucous metaplasia. These findings suggest progressive airway obstruction with an abnormal inflammatory response to TS exposure in this rodent model of COPD. We conclude a dysregulated immunologic response, along with airway inflammation are strongly associated with the impairment of physiological lung function in TS-exposed rats.

Background. Elevated levels of the cysteine protease cathepsin S (CatS) are associated with chronic mucoobstructive lung diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). We have previously demonstrated that prophylactic treatment with a CatS inhibitor from birth reduces inflammation, mucus plugging, and lung tissue damage in juvenile β-epithelial Na+ channel-overexpressing transgenic (βENaC-Tg) mice with chronic inflammatory mucoobstructive lung disease. In this study, we build upon this work to examine the effects of therapeutic intervention with a CatS inhibitor in adult βENaC-Tg mice with established disease. Methods. βENaC-Tg mice and wild-type (WT) littermates were treated with a CatS inhibitor from 4 to 6 weeks of age, and CatS-/-βENaC-Tg mice were analysed at 6 weeks of age. Bronchoalveolar lavage (BAL) fluid inflammatory cell counts were quantified, and lung tissue destruction and mucus obstruction were analysed histologically. Results. At 6 weeks of age, βENaC-Tg mice developed significant airway inflammation, lung tissue damage, and mucus plugging when compared to WT mice. CatS-/-βENaC-Tg mice and βENaC-Tg mice receiving inhibitor had significantly reduced airway mononuclear and polymorphonuclear (PMN) cell counts as well as mucus plugging. However, in contrast to CatS-/-βENaC-Tg mice, therapeutic inhibition of CatS in βENaC-Tg mice had no effect on established emphysema-like lung tissue damage. Conclusions. These results suggest that while early CatS targeting may be required to prevent the onset and progression of lung tissue damage, therapeutic CatS targeting effectively inhibited airway inflammation and mucus obstruction. These results indicate the important role CatS may play in the pathogenesis and progression of mucoobstructive lung disease.

Background: Therapeutic bronchoscopy (TB) is an accepted strategy for the symptomatic management of central airway malignant obstruction. Stent insertion is recommended in case of extrinsic compression, but its value in preventing airway re-obstruction after endobronchial treatment without extrinsic compression is unknown. Objective: Silicone stent Placement in symptomatic airway Obstruction due to non-small cell lung Cancer (SPOC) is the first randomized controlled trial investigating the potential benefit of silicone stent insertion after successful TB in symptomatic malignant airway obstruction without extrinsic compression. Method: We planned an inclusion of 170 patients in each group (stent or no stent) over a period of 3 years with 1-year follow-up. The 1-year survival rate without symptomatic local recurrence was the main endpoint. Recurrence rate, survival, quality of life, and stent tolerance were secondary endpoints. During 1-year follow-up, clinical events were monitored by flexible bronchoscopies and were evaluated by an independent expert committee. Results: Seventy-eight patients (mean age 65 years) were randomized into 2 arms: stents (n = 40) or no stents (n = 38) after IB. Consequently, our main endpoint could not be statistically answered. Improvement of dyspnea symptoms is noticeable in each group but lasts longer in the stent group. Stents do not change the survival curve but reduce unattended bronchoscopies. In the no stent group, 19 new TB were performed with 16 stents inserted contrasting with 10 rigid bronchoscopies and 3 stents placed in the stent group. In a subgroup analysis according to the oncologic management protocol following TB (firstline treatment and other lines or palliation), the beneficial effect of stenting on obstruction recurrence was highly significant (p < 0.002), but was not observed in the naïve group, free from first-line chemotherapy. Conclusion: Silicone stent placement maintains the benefit of TB after 1 year on dyspnea score, obstruction’s recurrence, and the need for new TB. Stenting does not affect the quality of life and is suggested for patients after failure of first-line chemotherapy. It is not suggested in patients without previous oncologic treatment.

Airway obstruction and pulmonary mechanics remain understudied despite lung disease being the third cause of death in the United States. Lack of relevant data has led computational pulmonary models to infer mechanical properties from available material data for the trachea. Additionally, the time-dependent, viscoelastic behaviors of airways have been largely overlooked, despite their potential physiological relevance and utility as metrics of tissue remodeling and disease progression. Here, we address the clear need for airway-specific material characterization to inform biophysical studies of the bronchial tree. Specimens from three airway levels (trachea, large bronchi, and small bronchi) and two orientations (axial and circumferential) were prepared from five fresh pig lungs. Uniaxial tensile tests revealed substantial heterogeneity and anisotropy. Overall, the linear pseudoelastic modulus was significantly higher axially than circumferentially (30.5 ± 3.1 vs. 8.4 ± 1.1 kPa) and significantly higher among circumferential samples for small bronchi than for the trachea and large bronchi (12.5 ± 1.9 vs. 6.0 ± 0.6 and 6.6 ± 0.9 kPa). Circumferential samples exhibited greater percent stress relaxation over 300 s than their axial counterparts (38.0 ± 1.4 vs. 23.1 ± 1.5%). Axial and circumferential trachea samples displayed greater percent stress relaxation (26.4 ± 1.6 and 42.5 ± 1.7%) than corresponding large and small bronchi. This ex vivo pseudoelastic and viscoelastic characterization reveals novel anisotropic and heterogeneous behaviors and equips us to construct airway-specific constitutive relations. Our results establish necessary fundamentals for airway mechanics, laying the groundwork for future studies to extend to clinical questions surrounding lung injury, and further directly enables computational tools for lung disease obstruction predictions. NEW & NOTEWORTHY Understanding the mechanics of the lung is necessary for investigating disease progression. Trachea mechanics comprises the vast majority of ex vivo airway tissue characterization despite distal airways being the site of disease manifestation and occlusion. Furthermore, viscoelastic studies are scarce, whereas time-dependent behaviors could be potential physiological metrics of tissue remodeling. In this study, the critical need for airway-specific material properties is addressed, reporting bronchial tree anisotropic and heterogeneous material properties.

Abstract Asthma is a chronic disease of the airways that has long been viewed predominately as an inflammatory condition. Accordingly, current therapeutic interventions focus primarily on resolving inflammation. However, the mainstay of asthma therapy neither fully improves lung function nor prevents disease exacerbations, suggesting involvement of other factors. An emerging concept now holds that airway remodeling, another major pathological feature of asthma, is as important as inflammation in asthma pathogenesis. Structural changes associated with asthma include disrupted epithelial integrity, subepithelial fibrosis, goblet cell hyperplasia/metaplasia, smooth muscle hypertrophy/hyperplasia, and enhanced vascularity. These alterations are hypothesized to contribute to airway hyperresponsiveness, airway obstruction, airflow limitation, and progressive decline of lung function in asthmatic individuals. Consequently, targeting inflammation alone does not suffice to provide optimal clinical benefits. Here we review asthmatic airway remodeling, focusing on airway epithelium, which is critical to maintaining a healthy respiratory system, and is the primary defense against inhaled irritants. In asthma, airway epithelium is both a mediator and target of inflammation, manifesting remodeling and resulting obstruction among its downstream effects. We also highlight the potential benefits of therapeutically targeting airway structural alterations. Since pathological tissue remodeling is likewise observed in other injury- and inflammation-prone tissues and organs, our discussion may have implications beyond asthma and lung disease.

Collapsible pharyngeal airway size is determined by interaction between structural properties of the pharyngeal airway and neural regulation of the pharyngeal dilating muscles. Obesity seems to have two distinct mechanical influences on the pharyngeal airway collapsibility. First, obesity increases soft tissue surrounding the pharyngeal airway within limited maxillomandible enclosure occupying and narrowing its space (pharyngeal anatomical imbalance). Second, obesity, particularly central obesity, increases visceral fat volume decreasing lung volume. Pharyngeal wall collapsibility is increased by the lung volume reduction, possibly through decreased longitudinal tracheal traction (lung volume hypothesis). Neural compensation for functioning structural abnormalities operating during wakefulness is lost during sleep, leading to pharyngeal obstruction. Instability of the negative feedback of the respiratory system may accelerate cycling of pharyngeal closure and opening. Improvement of the pharyngeal anatomical imbalance and maintenance of lung volume are the keys for safe perioperative airway managements of obese patients with obstructive sleep apnea.

Chronic bronchitis frequently leads to irreversible airway obstruction. Alteration of airway architecture with abnormal airway connective tissue is thought to play an important role in this process. We hypothesized that the epithelial cells that line the airways modulate the development of peribronchial fibrosis and fixed airway obstruction by directing fibroblast proliferation. To assess this, we examined stimulatory activities for human lung fibroblast proliferation in bovine bronchial epithelial cell-conditioned medium. The conditioned medium stimulated the proliferation of fibroblasts in a serum-free culture system in a concentration-dependent manner. The fibroblast growth stimulatory activity was heterogenous, with molecular masses of > 50 and approximately 10 kDa. Bronchial epithelial cell-conditioned medium also contained fibroblast growth inhibitory factors, including both transforming growth factor (TGF)-beta and, based on indomethacin sensitivity, cyclooxygenase products. TGF-beta appeared to contribute to the morphological change of fibroblasts induced by the conditioned medium. Co-culture of human lung fibroblasts with bronchial epithelial cells resulted in a stimulation of fibroblast proliferation. In summary, airway epithelial cells appear to regulate fibroblast proliferation and may play a role in peribronchial fibrosis in chronic bronchitis.

Argon plasma coagulation (APC) is one of the interventional pulmonology techniques primarily aimed at the treatment of hemoptysis. It represents a form of non contact electrosurgey that uses ionized argon gas in order to produce electrical current that affects soft tissues. APC is reported to be effective in the treatment of early stage lung cancer, in the treatment of benign granulation tissue surrounding tracheal stents and in palliative treatment of malignant airway obstruction. Major indication for APC is hemostasis in severe hemoptysis, it can also be used as an alternative technique for laser resection or electrocautery, in urgent removal of tumors situated in large airways. The present article reports successful use of APC in the treatment of centrally located squamous cell lung cancer that caused complete right lung atelectasis. The use of APC led to complete reexpansion of the right lung and improvement in dyspnoea and chest discomfort of the patient. Significant improvement was observed in lung function parameters and blood gas analysis. With the use of APC solid tumor was completely removed from the right main bronchus and airway integrity was restored. From this case we can conclude that APC can be safely and successfully used for urgent debulking of malignant central airway obstruction.

Objectives: The aim of our study is to report a case of a child with subglottic thymus that was suspected during diagnostic work-up for severe airway obstruction, excised surgically and confirmed with final histopathological examination. Moreover, we performed a narrative literature review to outline clinical and diagnostic features of this rare condition and to report suggestions for the management of subglottic masses. Methods: We report the case of a 7-month-old boy who was admitted to our Pediatric Airway Team Unit due to a history of worsening biphasic stridor and recurrent episodes of upper airway obstruction. The successful diagnostic work-up and a narrative literature of analogous cases of subglottic thymus were reported. Results: Ectopic thymus is a very rare condition in which thymic tissue is found outside the normal pathway of its embryonic migration. It usually presents as a cystic or, more rarely, solid mass, showing an indolent course toward spontaneous involution. In some cases, however, it becomes symptomatic exerting compression on surrounding vital structures. Due to its rarity, the initial diagnosis is normally mistaken with inflammatory diseases or malignancies and the definitive diagnosis is only achieved after histological examination of the excised specimen. To our knowledge, only four other cases of subglottic ectopic thymic tissue have been reported in the English literature so far and the diagnosis has never been suspected preoperatively. Conclusion: It is mandatory to consider ectopic thymic tissue in the differential diagnosis in children presenting with airways obstruction in order to prevent unnecessary, extensive, and exploratory surgery.

Immobility, fixation, or paralysis of the vocal folds is an ominous sign when encountered in the clinics. This may be due to a variety of diseases, lesions, injuries, or vascular compromise which may affect the integrity and physiologic mechanism of the vocal folds. The common etiologies include infectious processes such as laryngeal or pulmonary tuberculosis (PTB), malignancy or neoplasms, central problems such as cerebrovascular accidents (CVA), stroke and others.1,2,3 The problem should be addressed immediately because this potentially life threatening and imminent narrowing of the glottic opening may lead to respiratory distress. Vocal fold paralysis due to compression of the recurrent laryngeal nerve from PTB and laryngeal cancer are perennially seen in clinical practice, but immobility of the vocal folds due to cricoarytenoid joint fixation or ankylosis is seldom seen and appreciated.
 Hence, we present a case of bilateral cricoarytenoid joint ankylosis and discuss its etiology, pathophysiology, differential diagnoses, ancillary procedures, and management.
 
 CASE REPORT
 A 60-year-old man was admitted for the first time because of difficulty of breathing and stridor. One week prior to admission he started to experience difficult breathing associated with productive cough and colds. He consulted in a primary private hospital and was managed as a case of bronchial asthma in exacerbation. Nebulization with salbutamol afforded temporary relief.
 A few hours prior to admission, difficulty of breathing and productive cough worsened, prompting emergency room consult. He was referred to us for further evaluation of stridor.
 The patient had no diabetes mellitus, hypertension or allergies to food and drugs. He was diagnosed with refractory bronchial asthma during childhood and had frequent hospitalizations for pulmonary infections. He had no maintenance medication for bronchial asthma and was nebulized with salbutamol during exacerbations. He had PTB and completed six months’ anti-TB medications in 2013. The patient claimed that he had no dyspneic episodes during routine daily activities or upon exertion. No history of hoarseness or joint pain was noted either. A golf caddy, he was a previous 15-pack-year smoker, occasional alcoholic beverage drinker and denied use of illicit drugs.
 Upon admission, the patient was awake, coherent, not in cardiorespiratory distress. Blood pressure was 110/70 mmHg, pulse rate was 74/minute, respiration was tachypneic at 24 cycles per minute, afebrile. Ear examination showed normal pinnae, no tragal tenderness, patent external auditory canals with no discharge and 80-90% dry central perforations of both tympanic membranes. Anterior rhinoscopy, nasal endoscopy and the oral cavity examination were unremarkable. Head and neck examination showed no cervical lymphadenopathy or palpable mass.
 Video laryngoscopy showed both vocal folds were immobile and fixed in paramedian position upon inspiration, with a 1–2 mm glottic opening and no mass or lesion appreciated. (Figure 1)
 The initial impression was impending upper airway obstruction secondary to bilateral vocal fold paralysis. Under general anesthesia, direct laryngoscopy revealed no mass or lesion on both vocal folds and passive mobility test demonstrated resistance and limitation of lateral rotation and movement of the arytenoids on both sides. (Figure 2) The vocal folds did not abduct on lateral retraction of the arytenoids. Tracheostomy was performed and he was discharged after a few days.
 A subsequent laryngeal electromyography (EMG) study showed no signs of myopathy or acute or chronic denervation changes of the thyroarytenoid muscles, and rheumatoid factor was normal. At this point, bilateral cricoarytenoid fixation or ankylosis was considered and posterior interarytenoid web and bilateral vocal fold paralysis were ruled out. 
 We recommended a lateralization procedure such as unilateral arytenoidectomy with cordectomy. The patient is currently well while he and his family are still contemplating whether he will undergo the surgical procedure.
 
 DISCUSSION
 Respiratory stridor is always considered an ominous sign which implies upper airway obstruction. If severe, stridor may compromise breathing and in some instances is life threatening and a telltale sign of imminent danger requiring immediate endotracheal intubation. Stridor is a musical, high-pitched sound which may be elicited in the presence of laryngeal and upper tracheal obstruction while wheezes are defined as high-pitched, continuous, adventitious lung sounds.4,5
 Stridor may be due to several reasons such as immaturity of the laryngeal structures seen in laryngomalacia in newborns, laryngeal infection, foreign body in the airway, and chronic obstructive pulmonary disease.3,6 This may be the reason why bronchial asthma was entertained in the clinical course of our patient and initially at the emergency room. It is unfortunate that despite the non-responsiveness of bronchial asthma to medical therapy and persistence of stridor, no ENT referral to evaluate the upper airway was made until recently. It should be emphasized that patients who develop stridor need to be evaluated by otolaryngologists specifically to ascertain the status of the vocal folds, which in this case turned out to be fixed or ankylosed, a condition which is rarely seen and encountered in clinical practice.
 Among the differential diagnoses considered in this case were laryngeal cancer, vocal fold paralysis, interarytenoid web, and arthritis.7,8,9
 Initially, laryngeal cancer was entertained because of his age, however no mass or suspicious lesion was appreciated on video laryngoscopy and this was ruled out. Because the vocal folds were immobile and fixed in paramedian position upon inspiration, bilateral vocal fold paralysis was considered with the etiology to be determined.
 Vocal fold paralysis occurs when nerve impulses to the laryngeal muscles are disrupted in case of CVA or stroke, recurrent nerve injury after thyroid surgery or compression of the inferior laryngeal nerve due to pulmonary TB or lung cancer.8,11 On the other hand, vocal fold fixation occurs when movement of the cricoarytenoid joint is compromised in cases of rheumatoid arthritis provided that the innervation is intact.10,11
 Another common differential diagnosis which may be entertained is laryngeal TB in which nodular lesions may be seen in the vocal folds, granulation tissues are usually present in the posterior commissure and histopathology shows Langhans cells and caseation necrosis.8 Paralysis is oftentimes unilateral due to compression of the recurrent laryngeal nerve from apical PTB. Although the patient has a history of TB, he was asymptomatic and close examination of the vocal folds revealed no lesions except for bilateral fixation, and this was ruled out.
 Direct laryngoscopy (DL), the gold standard in the evaluation of laryngeal anatomy especially when dealing with the vocal folds,3 showed smooth, normal-looking vocal folds with no lesions. The passive mobility test is done to differentiate vocal fold paralysis from cricoarytenoid ankylosis, by retracting or pushing the arytenoid laterally. If there is limitation of rotation and movement of the arytenoid laterally and the vocal folds do not abduct, then cricoarytenoid ankylosis or fixation is considered. On the contrary, if the arytenoid rotates and abducts laterally when retracted by forceps, then vocal fold paralysis is considered.1,6 Hence, because there was limitation of rotation and movement of the arytenoids, cricoarytenoid joint fixation was entertained and vocal fold paralysis was ruled out.
 Interarytenoid web was excluded because the vocal folds had no mucosal adhesions, synechiae, or any scarring within the posterior portion of the glottis. In addition, although the patient’s glottic opening was restricted, no difficulty was encountered during endotracheal intubation since a smaller caliber tube was used.
 To further confirm the diagnosis of cricoarytenoid fixation, laryngeal electromyography (EMG) revealed no paralysis of the thyroarytenoid muscles with no signs of myopathy and acute or chronic denervation, making bilateral vocal fold paralysis unlikely in this case. Laryngeal EMG is indicated to determine the integrity of the laryngeal muscles and innervation especially in cases of vocal fold paralysis.11 In post-thyroidectomy patients, laryngeal EMG is done 6 months after surgery to determine if the laryngeal nerve injury may recover or is irreversible. The 6-month waiting period is to allow swelling or inflammation to subside and to observe whether the injured nerve will recover prior to further intervention.12
 The findings on direct laryngoscopy, passive mobility test and laryngeal electromyography clearly favor the diagnosis of cricoarytenoid joint ankylosis. Other ancillary procedures such as a CT scan may show sclerosis of the arytenoids1,11 in elderly patients and videostroboscopy may be useful in determining the relative vertical height and tension of the vocal folds for assessing the cricoarytenoid function.1 A CT scan was not done because there was no palpable neck mass and no other lesion was entertained that would warrant CT imaging. Videostroboscopy may help and may further show and magnify the movement of the vocal folds for observation however, the findings seen on direct laryngoscopy and laryngeal EMG were deemed enough to support and confirm the diagnosis.
 The patient may be classified under type IV posterior glottic stenosis - congenital or acquired bilateral cricoarytenoid fixation with or without interarytenoid scarring - based on the classification by Bogdasarian and Olson which was later modified by Irving and associates.3 Interarytenoid web and scarring presents as bilateral impaired abduction but adduction is normal and patients affected tend to have a normal voice while the main presenting symptom is airway compromise. In cricoarytenoid joint ankylosis, adduction and abduction of the vocal folds are limited.3 As previously mentioned, to distinguish cricoarytenoid joint ankylosis from vocal fold paralysis, palpation of the cricoarytenoid joint on rigid endoscopy and laryngeal EMG are necessary for definitive diagnosis.6
 The patient’s voice was normal because the vocal folds approximate each other with a 1 to 2 mm glottic opening while no history of aspiration was apparent because the vocal folds are fixed in paramedian position which may prevent fluid from entering the larynx during swallowing. Although the patient’s voice is normal, respiration is compromised manifested as stridor and difficulty of breathing requiring tracheostomy. 
 In contrast, patients with acute or recent unilateral vocal fold paralysis in post-thyroidectomy or post-CVA (stroke) conditions may initially manifest with aspiration. This is because the vocal fold assumes an intermediate position in which the glottic opening is relatively wider compared with the paramedian position. In a few months’ time, the paralyzed fold will compensate, move medially, and assume a paramedian position and aspiration may eventually resolve.13
 Cricoarytenoid ankylosis has several etiologies which include arthritides, bacterial infection and trauma. Rheumatoid arthritis may account for numerous clinical diagnoses of cricoarytenoid ankylosis.2 Other causes include gout, Reiter Syndrome, and ankylosing spondylitis. Some anecdotal evidence suggests a mump-associated laryngeal arthritis and fixation secondary to radiation therapy.2, 8 Bacterial involvement of the joint space with infectious microorganisms such as streptococcal species, with resultant ankylosis is also well established.8 External and direct laryngeal trauma may also result in cricoarytenoid joint injury.8 Documented and retrospective studies suggest intubation-related joint injury and posterior or anterior arytenoid displacement secondary to the distal tip of the endotracheal tube engaging the arytenoid during intubation.8 Traumatic obstetric delivery using forceps and postpartum newborn care through vigorous cleansing and suctioning the mouth and pharynx of the newborn are also mentioned in the literature.11 Posterior dislocation resulting from extubation with a partially inflated endotracheal tube cuff is another probable cause.7, 8 Another potential etiology is arytenoid chondritis secondary to prolonged endotracheal intubation, which results in fibrosis.8, 16 Reviewing the patient’s history, however, showed no history of trauma, previous intubation, signs and symptoms of arthritis and serious laryngeal infections. The patient was delivered via normal spontaneous delivery by a traditional birth attendant (“hilot”) and no apparent respiratory distress or postpartum hospitalization was known of by the patient.
 Cricoarytenoid ankylosis is usually associated with cases of rheumatoid arthritis with 17 to 33% incidence among RA patients.9 House et al. in 2010 described approximately 0.1% incidence of cricoarytenoid joint ankylosis in endotracheal intubations.16 Most cases of vocal fold immobility seen under the service is secondary to vocal fold paralysis due to cerebrovascular accident (stroke), pulmonary problems such as PTB, or laryngeal malignancy and to our knowledge, this is the first reported case of cricoarytenoid joint ankylosis in our institution. 
 Chronic cricoarytenoid joint ankylosis may be mistaken for asthma or chronic bronchitis, with symptoms of dyspnea, hoarseness, or stridor.3 In rheumatoid arthritis, laryngoscopy may show rough and thick mucosa and narrowed glottic chink which were contrary to the recent endoscopic findings. If the etiology is bacterial, there is direct involvement of the joint space with infectious agents, such as streptococcal species, which leads to scarring and thickening of the cricoarytenoid joints.8 Airway compromise occurs most commonly in patients with long-standing cricoarytenoid ankylosis and laryngeal stridor has been described as the sole presentation of the disease as manifested in this case.8, 14, 17 To rule out RA in this case, rheumatoid factor (RF) was done with negative results.
 
 Finally, when it comes to upper airway obstruction, the glottic opening or opening of the vocal folds should be thoroughly evaluated. The normal glottic opening in newborns opens approximately 4 mm in a lateral direction. Congenital subglottic stenosis is defined as a subglottic diameter of less than 4 mm.13 In retrospect, it may be presumed that the patient’s glottis may not be seriously compromised since birth because he was able to thrive and breathe with no apparent difficulty. It may be conjectured that narrowing of the glottic opening occurred only later in life. Although asymptomatic, rheumatoid factor was negative, and the etiology of the patient’s ankylosis remains perplexing and elusive.
 The management of cricoarytenoid ankylosis includes tracheostomy to address the upper airway obstruction. Surgical management includes open arytenoidectomy, arytenoidpexy and endoscopic arytenoidectomy or transverse cordectomy and all have their advantages and disadvantages.6, 11, 16 These are lateralization procedures which aim to widen the glottic opening and wean the patient from tracheostomy afterwards.
 In closing, when bronchial asthma remains refractory to treatment, the physician should not hesitate to refer to otolaryngologists to rule out other probable upper airway pathologies. Although rare, ankyloses of the cricoarytenoid joint should be considered especially when the movement of the vocal folds is compromised. Although direct laryngoscopy, passive mobility tests and laryngeal EMG are indispensable in clinching the diagnosis, the clinical history is important in determining etiology which in this case remains elusive and perplexing.
 
 
 
 
 
 
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The prevalence of obesity has increased dramatically worldwide, predisposing individuals to an increased risk of morbidity and mortality due to cardiovascular disease and type 2 diabetes. Less recognized is the fact that obesity may play a significant role in the pathogenesis of pulmonary diseases through mechanisms that may involve proinflammatory mediators produced in adipose tissue that contribute to a low-grade state of systemic inflammation. In animal models, inflammatory responses in the lung have been shown to influence the production of the adipocytokines, leptin and adiponectin, cytokines, acute phase proteins, and other mediators produced by adipose tissue that may participate in immune responses of the lung. An increased adipose tissue mass may also influence susceptibility to pulmonary infections, enhance pulmonary inflammation associated with environmental exposures, and exacerbate airway obstruction in preexisting lung disease. An increased understanding of the mechanisms by which obesity influences pulmonary inflammation may facilitate the development of novel therapeutic interventions for the treatment of lung disease.

Rationale: Some laryngeal masses are typically asymptomatic and easily ignored. However, they can be rare causes of unanticipated difficult airway, leading to critical situations such as “cannot ventilate” or “cannot ventilate and cannot intubate” during anesthesia induction. Inappropriate airway management in such scenarios can have catastrophic consequences for an anesthetized patient. Here we report a case of sudden, unanticipated difficult mask ventilation caused by an asymptomatic supraglottic mass during sedative induction, which was quickly and effectively relieved by the Heimlich maneuver and chest compression. Patient concerns: We report a rare case of airway crisis occurred during sedative induction in a 63-year-old patient scheduled for a routine flexible bronchoscopy, and no evidence of respiratory difficulty or signs of obstruction was found in preoperative evaluation. Diagnoses: A detailed examination of laryngopharyngeal structure under bronchoscopy revealed a supraglottic soft-tissue mass with a size of 1.6 × 0.8 cm covering the membranous part of the glottic area, which was the true cause of difficult mask ventilation in this patient during sedative induction. Interventions: As the unanticipated difficult mask ventilation occurred, 2-handed mask ventilation was initiated immediately for 9 attempts but failed. Fortunately, the airway crisis was successfully relieved with 2 Heimlich attempts and 3 chest compressions, and no need for a laryngeal mask airway. Outcomes: Once the airway crisis was relieved and the supraglottic mass was confirmed, the patient underwent a second sedative anesthesia and a successful laryngeal mask airway-assisted bronchoscopy, with no post-bronchoscopy adverse events. Lessons: Asymptomatic supraglottic masses can cause valve-like upper airway obstruction and lead to unanticipated difficult mask ventilation. The Heimlich maneuver and chest compression may be effective in such critical situations and can serve as an emergency intervention.

Within the airways, endothelin-1 (ET-1) can exert a range of prominent effects, including airway smooth muscle contraction, bronchial obstruction, airway wall edema, and airway remodeling. ET-1 also possesses proinflammatory properties and contributes to the late-phase response in allergic airways. However, there is no direct evidence for the contribution of endogenous ET-1 to airway hyperresponsiveness in allergic airways. Allergic inflammation induced in mice by sensitization and challenge with the house dust mite allergen Der P1 was associated with elevated levels of ET-1 within the lung, increased numbers of eosinophils within bronchoalveolar lavage fluid and tissue sections, and development of airway hyperresponsiveness to methacholine ( P < 0.05, n = 6 mice per group). Treatment of allergic mice with an endothelin receptor antagonist, SB-217242 (30 mg · kg−1· day−1), during allergen challenge markedly inhibited airway eosinophilia (bronchoalveolar lavage fluid and tissue) and development of airway hyperresponsiveness. These findings provide direct evidence for a mediator role for ET-1 in development of airway hyperresponsiveness and airway eosinophilia in Der P1-sensitized mice after antigen challenge.

Introduction: Air pollution can cause respiratory system disorders in the form of alveoli damage, airway, and lung tissue inflammation. Inflammation of the lungs can damage the respiratory tissue and stimulate excess sputum production which causes ineffective airway clearance. This process, if it takes a long time, causes irreversible structural damage to the airway wall. This condition can progress to severe airway obstruction, called COPD. This research aims to explain nursing care for patients with Chronic Obstructive Pulmonary Disease (COPD) in the Tuberose Room at RSI Nashrul Ummah Lamongan. Methods: The research design used in this research is case study research. Participants in the study for Mr. "K" 69 years. The result of problem identification that arises is Chronic Obstructive Pulmonary Disease (COPD) with the main nursing diagnosis of Ineffective Airway Cleansing. Interventions that were emphasized and carried out in the field in cases were maintaining oxygen therapy, semi-fowler position, and administration of a nebulizer. The final evaluation of nursing diagnoses in patients was not resolved within the specified time. Result: Implementation of Nursing Care Ineffective Airway Cleansing of COPD patients in the Tuberose Room at RSI Nashrul Ummah Lamongan, there are still gaps with the literature. Conclusion: Suggestions for nurses are expected to be the focus of nurses in developing science to be applied to all nursing personnel in providing nursing care to ineffective airway cleaning for COPD patients.

Asthma is an inflammatory disease of the respiratory system characterized by cough, shortness of breath, wheezing, sputum, obstruction and bronchial hyperactivity. Asthma leads to disruption of epithelial structure, subepithelial fibrosis, inflammation, and ultimately airway reorganization. MSCs migrate into inflammatory tissue and settle there. Once in the tissue, the MSCs suppress inflammation and improve the internal structure of the tissue. These effects are achieved by transforming into tissue cells, producing anti-inflammatory and growth factors, and releasing microRNAs and extracellular vesicles. The effect of MSCs on asthma is based mostly on in vivo experimental animal models and in vitro studies of airway cells. While ovalbumin, cockroach extract and house dust mite are mostly used for in vivo experimental animal models, airway smooth muscle cells are mostly used for in vivo studies. This study aims to objectively present the information obtained from reliable articles about whether MSCs can be used in the treatment of asthma, a chronic inflammatory lung disease.

Pharmacologic agonism of the β2-adrenergic receptor (β2AR) induces bronchodilation by activating the enzyme adenylyl cyclase to generate cyclic adenosine monophosphate (cAMP). β2AR agonists are generally the most effective strategy to relieve acute airway obstruction in asthmatic patients, but they are much less effective when airway obstruction in young patients is triggered by infection with respiratory syncytial virus (RSV). Here, we investigated the effects of RSV infection on the abundance and function of β2AR in primary human airway smooth muscle cells (HASMCs) derived from pediatric lung tissue. We showed that RSV infection of HASMCs resulted in proteolytic cleavage of β2AR mediated by the proteasome. RSV infection also resulted in β2AR ligand–independent activation of adenylyl cyclase, leading to reduced cAMP synthesis compared to that in uninfected control cells. Last, RSV infection caused stronger airway smooth muscle cell contraction in vitro due to increased cytosolic Ca2+ concentrations. Thus, our results suggest that RSV infection simultaneously induces loss of functional β2ARs and activation of multiple pathways favoring airway obstruction in young patients, with the net effect of counteracting β2AR agonist–induced bronchodilation. These findings not only provide a potential mechanism for the reported lack of clinical efficacy of β2AR agonists for treating virus-induced wheezing but also open the path to developing more precise therapeutic strategies.

Asthma is a heterogeneous disease with ranging etiology and severity. Asthma is a disease of chronic inflammation of the airways, with clinical symptoms of wheezing, breathlessness, cough, and chest tightness manifested as chronic fixed or variable airflow obstruction and airway hyperresponsiveness that predispose the airway epithelium to repeated injury, repair, and regeneration. In recent years, innate lymphoid cells (ILC1, ILC2, and ILC3) have been discovered. The predominant ILC type found in the lung tissue is group 2 innate lymphoid cells (ILC2s). Upon damage to the airway epithelium mediating the release of epithelial cytokines (TSLP, IL-33, and IL-25) ensued the activation of ILC2 in an antigen-independent manner. Activated ILC2 produces a significant amount of type 2 cytokines (IL-4, IL-5, IL-9, and IL-13), altogether contributing to type 2 inflammation in the airways. ILC2s are mediators of type 2 immunity for many type 2 inflammatory diseases such as asthma, since ILC2s were reported to play an important role in asthma pathogenesis. Here we discuss the role of ILC2 in the development of asthma and ILC2 effector cytokines (IL-4, IL-5, and IL-13) contributing to airway epithelial structural changes.

Chronic obstructive pulmonary disease (COPD) is characterized by abnormal repair in the lung resulting in airway obstruction associated with emphysema and peripheral airway fibrosis. Because the presence and degree of airways disease and emphysema varies between COPD patients, this may explain the heterogeneity in the response to treatment. It is currently unknown whether and to what extent inhaled steroids can affect the abnormal repair process in the airways and lung parenchyma in COPD. We investigated the effects of fluticasone on transforming growth factor (TGF)-β- and cigarette smoke-induced changes in mothers against decapentaplegic homolog (Smad) signaling and extracellular matrix (ECM) production in airway and parenchymal lung fibroblasts from patients with severe COPD. We showed that TGF-β-induced ECM production by pulmonary fibroblasts, but not activation of the Smad pathway, was sensitive to the effects of fluticasone. Fluticasone induced decorin production by airway fibroblasts and partly reversed the negative effects of TGF-β treatment. Fluticasone inhibited biglycan production in both airway and parenchymal fibroblasts and procollagen 1 production only in parenchymal fibroblasts, thereby restoring the basal difference in procollagen 1 production between airway and parenchymal fibroblasts. Our findings suggest that the effects of steroids on the airway compartment may be beneficial for patients with severe COPD, i.e., restoration of decorin loss around the airways, whereas the effects of steroids on the parenchyma may be detrimental, since the tissue repair response, i.e., biglycan and procollagen production, is inhibited. More research is needed to further disentangle these differential effects of steroid treatment on the different lung compartments and its impact on tissue repair and remodeling in COPD.

When a compressive impact load is applied on the chest, as in automobile crash or bomb explosion, the lung may be injured and show evidences of edema and hemorrhage. Since soft tissues have good strength in compression, why does a compression wave cause edema? Our hypothesis is that tensile and shear stresses are induced in the alveolar wall on rebound from compression, and that the maximum principal stress (tensile) may exceed critical values for increased permeability of the epithelium to small solutes, or even fracture. Furthermore, small airways may collapse and trap gas in alveoli at a critical strain, causing traumatic atelectasis. The collapsed airways reopen at a higher strain after the wave passes, during which the expansion of the trapped gas will induce additional tension in the alveolar wall. To test this hypothesis, we made three new experiments: (1), measuring the effect of transient overstretch of the alveolar membrane on the rate of lung weight increase; (2) determining the critical pressure for reopening collapsed airways of rabbit lung subjected to cyclic compression and expansion; (3) cyclic compression of lung with trachea closed. We found that in isolated rabbit lung overstretching increases the rate of edema fluid formation, that the critical strain for airway reopening is higher than that for closing, and that these critical strains are strain-rate dependent, but independent of the state of the trachea, whether it is open or closed. Furthermore, a theoretical analysis is presented to show that the maximum principal (tensile) stress is of the same order of magnitude as the maximum initial compressive stress at certain localities of the lung. All these support the hypothesis. But the experiments were done at too low a strain rate, and further work is needed.

Although both asthmatics and allergic rhinitics develop an acute inflammatory response to lower airway allergen challenge, only asthmatics experience airway obstruction resulting from chronic environmental allergen exposure. Hypothesizing that asthmatic airways have an altered response to chronic allergic inflammation, we compared the effects of repeated low-level exposures to inhaled Alternaria extract in sensitized rats with preexisting chronic postbronchiolitis airway dysfunction versus sensitized controls with normal airways. Measurements of air space (bronchoalveolar lavage) inflammatory cells, airway goblet cells, airway wall collagen, airway wall eosinophils, airway alveolar attachments, and pulmonary physiology were conducted after six weekly exposures to aerosolized saline or Alternaria extract. Postbronchiolitis rats, but not those starting with normal airways, had persistent increases in airway wall eosinophils, goblet cell hyperplasia in small airways, and loss of lung elastic recoil after repeated exposure to aerosolized Alternaria extract. Despite having elevated airway wall eosinophils, the postbronchiolitis rats had no eosinophils in bronchoalveolar lavage at 5 days after the last allergen exposure, suggesting altered egression of tissue eosinophils into the air space. In conclusion, rats with preexisting airway pathology had altered eosinophil trafficking and allergen-induced changes in airway epithelium and lung mechanics that were absent in sensitized control rats that had normal airways before the allergen exposures.

Perioperative management of patients with mediastinal masses still poses a challenge for the anesthesiologist, as the use of general anesthesia can be associated with acute perioperative cardiorespiratory impairment resulting from the mass collapsing on the airway or vascular structures. Dexmedetomidine can be used for procedural sedation due to its reversible sedative and anxiolytic properties with dose-dependent effects, while not interfering with ventilatory drive. These features are of particular interest for the perioperative management of patients with large anterior mediastinal masses. In this case, we report our anesthetic management of a 22-year-old male scheduled for anterior mediastinotomy, with a large anterior mediastinal mass, with 50% distal tracheal compression and marked collapse of the superior vena cava and brachiocephalic trunk. In the operation theatre, an infusion of dexmedetomidine was titrated to adequate anesthetic depth while keeping the patient under spontaneous ventilation with oxygen (O2) supplementation and local anesthetic infiltration of the surgical site. Mediastinotomy lasted for about 30 minutes, during which the patient maintained appropriate ventilation and hemodynamic stability. No adverse events occurred perioperatively. Diagnostic procedures such as mediastinotomy for tissue biopsy are necessary to achieve a histological diagnosis. High-risk patients may present with severe postural symptoms, stridor, cyanosis, and radiological evidence of more than 50% airway obstruction, tracheal compression with bronchial compression, pericardial effusion, or superior vena cava syndrome. Relaxation of bronchial smooth muscles under general anesthesia increases the risk of airway obstruction. In this case, with the use of dexmedetomidine combined with local anesthetic infiltration, spontaneous ventilation and muscle tone were preserved, decreasing the probability of intraoperative complications. It is our opinion that dexmedetomidine combined with local anesthetic infiltration can be a safe option for procedural sedation in patients presenting with high-risk anterior mediastinal masses for mediastinotomy.

Bronchial stenoses are one of the most common airways complications after lung transplantation. One of the main methods to restore airway patency is bronchial stenting. However, bronchial stenting is associated with a number of complications, such as stent migration, granulation tissue formation along the proximal and distal edges, and mucus obstruction of the lumen. This article demonstrates the possibility of manufacturing an everolimus-eluting stent from thermoplastic polyurethane and polylactide using 3D printing.

Air trapping due to airway closure has been associated with unstable asthma. In addition to airway closure that occurs at lower lung volumes during slow expiration, there may be further closure during a forced expiration because of airway compression. The purpose of this study was to define a reference range from a nonasthmatic population and investigate the characteristics of compressive air trapping in asthma. Spirometry and plethysmography were performed in 117 nonasthmatic subjects (ages 18–87 yr) and 153 asthma subjects (ages 12–72 yr). Air trapping was assessed as residual lung volume and the ratio of forced expiratory vital capacity (FVC) to slow inspiratory vital capacity (iVC) (FVC/iVC). There were no significant age or sex effects on the FVC/iVC ratio in the nonasthmatic subjects, and a fifth percentile lower limit of normal (LLN) of 0.93 was computed. An FVC/iVC ratio less than LLN defined compressive air trapping. Asthma subjects exhibited an age-related decline in the FVC/iVC ratio of 0.0027 per year ( P < 0.0001) in a mixed effects model, with additional decreases associated with severe asthma and male sex. FVC/iVC ratios< LLN were infrequent in subjects <30 yr but evident in most asthma subjects >50 yr. Lung residual volumes followed similar patterns of greater elevations in subjects with severe asthma, older age, and male sex. Compressive air trapping occurs frequently in older asthmatics, appearing to be a feature of the natural history of asthma that is greater in severe asthma and men. This component of premature airway closure affects spirometric assessment of airway function and may contribute to asthma symptoms during physical exertion. NEW & NOTEWORTHY Premature airway closure during exhalation is a component of airway obstruction that is associated with asthma severity and instability. Compressive air trapping is airway closure that is more extensive during a forced exhalation than with a slow, passive exhalation. We report that compressive air trapping occurs in most people > 50 yr with asthma, affects men more than women, and persists after bronchodilator treatment. This component of obstruction appears to be part of the natural history of asthma.

A 23-year-old female immigrant from Ethiopia presented with a history of hemoptysis and an abnormal chest x-ray. A computed tomography scan showed that her left lung was greatly shrunken and her right lung was very large but structurally normal. She had a history of multiple respiratory infections as a young child but had been well since the age of five years. Her lung function was within normal limits except for an increased residual volume. It is very likely that her left lung was destroyed early in childhood and that her right lung underwent compensatory growth. She did not show airways obstruction, which is usually seen when compensatory lung growth occurs after surgical removal of lung tissue; this may indicate that, in those cases, the surgery compromised airway function.

Peslin, R., and C. Duvivier. Partitioning of airway and respiratory tissue mechanical impedances by body plethysmography. J. Appl. Physiol. 84(2): 553–561, 1998.—We have tested the feasibility of separating the airway (Zaw) and tissue (Zti) components of total respiratory input impedance (Zrs,in) in healthy subjects by measuring alveolar gas compression by body plethysmography (Vpl) during pressure oscillations at the airway opening. The forced oscillation setup was placed inside a body plethysmograph, and the subjects rebreathedbtps gas. Zrs,in and the relationship between Vpl and airway flow (Hpl) were measured from 4 to 29 Hz. Zaw and Zti were computed from Zrs,in and Hpl by using the monoalveolar T-network model and alveolar gas compliance derived from thoracic gas volume. The data were in good agreement with previous observations: airway and tissue resistance exhibited some positive and negative frequency dependences, respectively; airway reactance was consistent with an inertance of 0.015 ± 0.003 hPa ⋅ s2 ⋅ l−1and tissue reactance with an elastance of 36 ± 8 hPa/l. The changes seen with varying lung volume, during elastic loading of the chest and during bronchoconstriction, were mostly in agreement with the expected effects. The data, as well as computer simulation, suggest that the partitioning is unaffected by mechanical inhomogeneity and only moderately affected by airway wall shunting.

Bronchiolitis obliterans syndrome (BOS) is the most common form of CLAD and is characterized by airflow limitation and an obstructive spirometric pattern without high-resolution computed tomography (HRCT) evidence of parenchymal opacities. Computed tomography and microCT analysis show abundant small airway obstruction, starting from the fifth generation of airway branching and affecting up to 40–70% of airways. The pathogenesis of BOS remains unclear. It is a multifactorial syndrome that leads to pathological tissue changes and clinical manifestations. Because BOS is associated with the worst long-term survival in LTx patients, many studies are focused on the early identification of BOS. Markers may be useful for diagnosis and for understanding the molecular and immunological mechanisms involved in the onset of BOS. Diagnostic and predictive markers of BOS have also been investigated in various biological materials, such as blood, BAL, lung tissue and extracellular vesicles. The aim of this review was to evaluate the scientific literature on markers of BOS after lung transplant. We performed a systematic review to find all available data on potential prognostic and diagnostic markers of BOS.

Glucagon is a hyperglycemic pancreatic hormone that has been shown to provide a beneficial effect against asthmatic bronchospasm. We investigated the role of this hormone on airway smooth muscle contraction and lung inflammation using bothin vitroandin vivoapproaches. The action of glucagon on mouse cholinergic tracheal contraction was studied in a conventional organ bath system, and its effect on airway obstruction was also investigated using the whole-body pletysmographic technique in mice. We also tested the effect of glucagon on lipopolysaccharide (LPS)-induced airway hyperreactivity (AHR) and inflammation. The expression of glucagon receptor (GcgR), CREB, phospho-CREB, nitric oxide synthase (NOS)-3, pNOS-3 and cyclooxygenase (COX)-1 was evaluated by western blot, while prostaglandin E2(PGE2) and tumour necrosis factor-α were quantified by enzyme-linked immunoassay and ELISA respectively. Glucagon partially inhibited carbachol-induced tracheal contraction in a mechanism clearly sensitive to des-His1-[Glu9]-glucagon amide, a GcgR antagonist. Remarkably, GcgR was more expressed in the lung and trachea with intact epithelium than in the epithelium-denuded trachea. In addition, the glucagon-mediated impairment of carbachol-induced contraction was prevented by either removing epithelial cells or blocking NOS (l-NAME), COX (indomethacin) or COX-1 (SC-560). In contrast, inhibitors of either heme oxygenase or COX-2 were inactive. Intranasal instillation of glucagon inhibited methacholine-induced airway obstruction by a mechanism sensitive to pretreatment withl-NAME, indomethacin and SC-560. Glucagon induced CREB and NOS-3 phosphorylation and increased PGE2levels in the lung tissue without altering COX-1 expression. Glucagon also inhibited LPS-induced AHR and bronchoalveolar inflammation. These findings suggest that glucagon possesses airway-relaxing properties that are mediated by epithelium-NOS-3-NO- and COX-1-PGE2-dependent mechanisms.

Airway compression is a common complication of TB lymphadenopathy in children, and the diagnostic workup of patients with suspected tracheal or bronchial stenoses includes bronchoscopy and CT (computed tomography).2 This process affords the opportunity to study aspects of CT relating to airway stenosis. Axial CT scans produce excellent resolution in the horizontal plane, but the extent of airway disease may be underestimated if only axial images are obtained.
 
 An advantage of using multidetector CT (MDCT) is the use of multiplanar reconstruction (MPR) to align the image along the longitudinal axis of the airway. There is also uncertainty if window settings affect the measurement of the airway diameter.
 
 We wished to determine if there was a significant difference between the measurements of compressed airway diameter in the axial plane compared with measurements of diameter using MPR for determining longitudinal axis of the airway; and to evaluate how measurements on lung window settings compare with soft tissue window settings.

Airway inflammation in asthma is related to increased reactive oxygen species generation, potentially leading to tissue injury and subsequent airway remodeling. We evaluated oxidative stress in peripheral blood from asthmatic subjects (n = 74) and matched controls (n = 65), using recently developed real-time monitoring of the protein hydroperoxide (HP) formation by the coumarin boronic acid (CBA) assay. We also investigated the relation of the systemic oxidative stress response in asthma to disease severity, lung function, airway remodeling indices (lung computed tomography and histology), and blood and bronchoalveolar lavage fluid (BAL) inflammatory biomarkers. We documented enhanced systemic oxidative stress in asthma, reflected by 35% faster and 58% higher cumulative fluorescent product generation in the CBA assay (p < 0.001 for both). The dynamics of HP generation correlated inversely with lung function but not with asthma severity or histological measures of airway remodeling. HP generation was associated positively with inflammatory indices in the blood (e.g., C-reactive protein) and BAL (e.g., interleukin [IL]-6, IL-12p70, and neutrophil count). Bronchial obstruction, thicker airway walls, increased BAL IL-6, and citrullinated histone 3 in systemic circulation independently determined increased HP formation. In conclusion, a real-time CBA assay showed increased systemic HP generation in asthma. In addition, it was associated with inflammatory biomarkers, suggesting that proper disease control can also lead to a decrease in oxidative stress.

A recent study, based on a combination of multidetector computed tomography scanning of an intact specimen with microcomputed tomography and histological analysis of lung tissue samples, reported that the number of terminal bronchioles were reduced from approximately 44,500/lung pair in control (donor) lungs to approximately 4800/lung pair in lungs donated by individuals with very severe (Global initiative for chronic Obstructive Lung Disease stage 4) chronic obstructive pulmonary disease (COPD) treated by lung transplantation. The present short review discusses the hypothesis that a rapid rate of terminal bronchiolar destruction causes the rapid decline in lung function leading to advanced COPD. With respect to why the terminal bronchioles are targeted for destruction, the postulated mechanisms of this destruction and the possibility that new treatments are able to either prevent or reverse the underlying cause of airway obstruction in COPD are addressed.

Background: Asthma is a chronic inflammatory disease affecting smaller airways. Airflow obstruction leading to airway hyper-responsiveness and increased mucus production are salient features of asthma pathophysiology. Generally, Th2 cytokines are increased in allergic asthma. Aim: To propose the molecular mechanisms by which Carica Papaya Leaves Extract (CPLE) alleviates pulmonary edema in animal model of allergic airway inflammation comparable to methylprednisolone. Place and duration of study: Pharmacology Department, University of Health Sciences Lahore for 1 year. Methods: We took twenty four male BALB/c mice and divided them equally into four groups. The control group was given PBS only, while Group II served as diseased group and induced airway inflammation by ovalbumin. Group III and IV were first induced with airway inflammation and side by side treated with Carica papaya leaf extract (CPLE) 100mg/kg body weight orally and methylprednisolone 15 mg/kg body weight intraperitoneally for seven consecutive days respectively. At the end of the experimental protocol, mice were euthanized and lung wet/dry ratio was measured. mRNA expression of AQP1 and AQP5 in lung tissue were also determined using RT-PCR. Results: Ethanolic extract of Carica Papaya leaves decreased all markers of pulmonary edema in mouse model of allergic airway inflammation comparable to methylprednisolone by decreasing lung wet/dry ratio and enhancing AQP1 and AQP5 mRNA expression. Conclusion: Carica Papaya leaves extract may diminish pulmonary edema in mice associated with allergic asthma. Keywords: AQP1, AQP5 (Aquaporins), Carica Papaya Leaves Extract (CPLE), Pulmonary Edema, Th2 cytokines.

OBJECTIVE: To investigate the short term effects of high frequency chest compression (HFCC) on several indices of respiratory system mechanics in normal subjects and patients with cystic fibrosis (CF).DESIGN: Comparative physiological approach. Subjects were blinded to 10 randomized HFCC settings (5, 10, 15, 20 and 25 Hz) with each applied at the lowest and at the highest background vest pressure.SETTING: Pulmonary function and lung mechanics laboratory, University of Alberta.PARTICIPANTS: Ten normal male volunteers (24.2±3.8 years) and 11 clinically stable CF patients (23.4±6.7 years). Normal subjects were nonsmokers who had normal lung function. The CF patients had a wide range of airway obstruction.INTERVENTIONS: HFCC was supplied by oscillating a pneumatic vest that covered the entire torso. Balloon tipped catheters were used to measure esophageal (Pes) and external chest wall (Pew) pressures. Changes in end-expiratory lung volume (EELV) during HFCC were measured from a spirogram and were compared with baseline functional residual capacity (FRC). The HFCC induced air movement al the mouth, oscillated tidal volume (Vosc), was measured by reverse plethysmography.RESULTS: Both normals and CF patients had similar changes in Pes and EELV. At the highest background vest pressure and at the higher oscillation frequencies, EELV decreased approximately 30% from the no-HFCC baseline FRC. Vosc decreased with increasing oscillation frequency but normals had higher Vosc than CF patients at each frequency. Conversion of Vose to flow (V˙osc) revealed that the highest Vosc occurred between 10 and 15 Hz for both normals and CF patients. Also, Vosc was dependent on the overall airway function. Low forced expired volume in 1 s resulted in low Vosc, especially when Vosc was measured during spontaneous expiration.CONCLUSIONS: CF patients with moderate or severe airway obstruction may gain maximal benefit from HFCC therapy when low vest pressure is used at an oscillation frequency of 10 to 15 Hz. The low vest pressure minimizes the decrease in EELV and 10 to 15 Hz maximizes Vosc.

Since the COVID-19 pandemic, the utilization of transthoracic ultrasonography (TTU) in the evaluation of pulmonary field artefacts has become standard practice among clinicians. However, there is a considerable lack of knowledge regarding the assessment of diaphragm mobility in the context of various lung diseases. Although numerous conditions are known to affect diaphragm mobility, including neurological, cardiovascular, and infectious diseases, it appears that pulmonary diseases may also limit the mobility of this major respiratory muscle. Despite the evidence of diaphragm mobility disorders in patients diagnosed with lung cancer, there is a discrepancy in the literature regarding the function of the diaphragm in individuals with chronic obstructive pulmonary disease (COPD). A shared aetiological factor frequently results in the co-occurrence of the aforementioned diseases. It is, however, possible to detect patients whose obstructive airway disease is caused only by the compression of infiltrative and nodal lesions rather than COPD. Bilateral TTU of diaphragmatic mobility in correlation with other available pulmonary function tests and radiological imaging may prove to be a valuable approach to isolating lung cancer patients with COPD overdiagnosis. Conversely, the overdiagnosis of COPD has been implicated in the potentially unnecessary and harmful use of inhaled medications with their adverse effects (e.g., cardiac arrhythmias, limb tremor, cough, and pneumonia), the failure to decrease obstruction in cases of other lung disorders, and the potential to contribute to the delayed diagnosis of the underlying condition responsible for the respiratory symptoms. This paper aims to provide a comprehensive overview of the utilization of ultrasound in the evaluation of diaphragm movement impairments for the detection of obstructions while also delineating the underlying limitations of this technique. Moreover, we propose a diagnostic algorithm for the purpose of excluding unilateral obstruction resulting from infiltrative neoplastic masses based on the ultrasound assessment of diaphragmatic mobility.

Asthmatic smokers have poor symptom control and accelerated decline in lung function. A reduced ratio of matrix metalloproteinase (MMP)-9/tissue inhibitors of metalloproteinases (TIMPs) in nonsmokers with asthma has been implicated in airway remodelling. We tested the hypothesis that sputum MMP-9 activity/TIMPs ratios are reduced in smokers compared with never-smokers with asthma and are associated with reduced lung function and altered computed tomography (CT) measures of airway wall dimensions.Lung function, airway dimensions by CT, and induced sputum concentrations (and activity) of MMP-9 and TIMP-1 and -2 were measured in 81 asthmatics and 43 healthy subjects (smokers and never-smokers). Respiratory epithelial MMP9 and TIMP mRNA was quantified in 31 severe asthmatics and 32 healthy controls.Sputum MMP-9 activity/TIMP-1 and TIMP-2 ratios, and nasal epithelial MMP9/TIMP1 and MMP9/TIMP2 expression ratios were reduced in smokers with asthma compared with never-smokers with asthma. Low sputum ratios in asthmatic smokers were associated with reduced post-bronchodilator forced expiratory volume in 1 s (FEV1), FEV1/forced vital capacity ratio and segmental airway lumen area.The association of a low sputum MMP-9 activity/TIMP-1 ratio with persistent airflow obstruction and reduced CT airway lumen area in smokers with asthma may indicate that an imbalance of MMP-9 and TIMPs contributes to structural changes to the airways in this group.

The volume fraction of extracellular matrix (ECM) within the layer of airway smooth muscle (ASM) is increased in subjects with fixed airflow obstruction. We postulated that changes in ECM within the ASM layer will impact force transmission during induced contraction and/or in response to externally applied stresses like a deep inspiration (DI). Subjects were patients undergoing lung resection surgery who were categorized as unobstructed ( n = 12) or “fixed” obstructed ( n = 6) on the basis of preoperative spirometry. The response to a DI, assessed by the ratio of isovolumic flows from maximal and partial inspirations (M/P), was also measured preoperatively. M/P was reduced in the obstructed group ( P = 0.02). Postoperatively, bronchial segments were obtained from resected tissue, and luminal narrowing to acetylcholine and bronchodilation to simulated DI were assessed in vitro. Airway wall dimensions and the volume fraction of ECM within the ASM were quantified. Maximal airway narrowing to acetylcholine ( P = 0.01) and the volume fraction of ECM within the ASM layer ( P = 0.02) were increased in the obstructed group, without a change in ASM thickness. Whereas bronchodilation to simulated DI in vitro was not different between obstructed and unobstructed groups, it was correlated with increased M/P (bronchodilation/less bronchoconstriction) in vivo ( P = 0.03). The volume fraction of ECM was inversely related to forced expiratory volume in 1 s FEV1 %predicted ( P = 0.04) and M/P ( P = 0.01). Results show that in subjects with fixed airflow obstruction the mechanical behavior of the airway wall is altered and there is a contemporaneous shift in the structural composition of the ASM layer. NEW & NOTEWORTHY Cartilaginous airways from subjects with fixed airflow obstruction have an increase in the volume fraction of extracellular matrix within the airway smooth muscle layer. These airways are also intrinsically more reactive to a contractile stimulus, which is expected to contribute to airway hyperresponsiveness in this population, often attributed to geometric mechanisms. In view of these results, we speculate on how changes in extracellular matrix may impact airway mechanics.

Airway hyperresponsiveness, airway inflammation, and reversible airway obstruction are physiological hallmarks of asthma. These responses are increasingly being studied in murine models of antigen exposure and challenge, using whole body plethysmography to noninvasively assess airway hyperresponsiveness. This approach infrequently has been correlated with indexes of airway hyperresponsiveness measured by invasive means. Furthermore, correlation with quantitative histological data for tissue infiltration by inflammatory and immune cells, particularly in the wall of airways, during daily airway challenge is lacking. To address these uncertainties, we used C57BL/6 mice that were immunized with ovalbumin or vehicle (saline) and sensitized to aerosolized ovalbumin or vehicle 8 days later. The mice were subsequently exposed to aerosolized ovalbumin or vehicle, respectively, on days 14–22. We assessed airway hyperresponsiveness to methacholine noninvasively on days 14, 15, 18, or 22; we studied the same mice 24 h later while they were anesthetized for invasive analyses of airway hyperresponsiveness. Plasma total IgE concentration was significantly higher in the ovalbumin-treated mice compared with the vehicle-treated mice, but this did not correlate with eosinophil number. Peak airway hyperresponsiveness measured by either approach correlated early during daily antigen challenge ( days 14 and 15), but this correlation was lost later during subsequent daily antigen challenges ( days 18 and 22). On days 14 and 15, peak airway hyperresponsiveness correlated with transmigration of neutrophils and macrophages, but not lymphocytes, in the peribronchovascular connective tissue sheaths. This extravascular accumulation was found to be focal by three-dimensional microscopy. We conclude that, although ovalbumin treatment changed lung function in mice, correlation between noninvasive and invasive measures of peak airway hyperresponsiveness was inconsistent.

Most cystic fibrosis (CF) patients die of lung failure, due to the combined effects of bacterial infection, neutrophil-mediated inflammation, and airway obstruction by hyperviscous mucus. To this day, it remains unclear where and how this pathological vicious circle is initiated in vivo. In particular, it has proven difficult to investigate whether inflammatory pathways are dysregulated in CF airways independently of infection. Also, the relative involvement of large (tracheobronchial) vs. small (bronchiolar) airways in CF pathophysiology is still unclear. To help address these issues, we used an in vivo model based on the maturation of human fetal CF and non-CF small airways in severe combined immunodeficiency mice. We show that uninfected mature CF small airway grafts, but not matched non-CF controls, undergo time-dependent neutrophil-mediated inflammation, leading to progressive lung tissue destruction. This model of mature human small airways provides the first clear-cut evidence that, in CF, inflammation may arise at least partly from a primary defect in the regulation of neutrophil recruitment, independently of infection.

AbstractEtiologies of fetal lung anomalies include congenital pulmonary airway malformation (CPAM), intra- or extralobar pulmonary sequestration, congenital high airway obstruction syndrome (CHAOS), bronchogenic cyst, and bronchial atresia. Fetal tracheobronchoscopy has been reported both as a diagnostic and therapeutic procedure in the setting of severe congenital lung lesions. In this case report, prenatal imaging of a fetus with a large chest mass was suspicious for an obstructive bronchial lesion. The absence of visible normal lung tissue on the right side and mass effect on the left side raised the concern for pulmonary hypoplasia. After antenatal betamethasone and a period observation, hydropic changes developed. Fetal tracheobronchoscopy was then performed in an effort to identify and decompress the suspected obstructive bronchial lesion. Other than release of bronchial debris, no anatomical abnormalities were visualized. However, the right lung lesion and mediastinal shift both decreased after the fetal bronchoscopy. The newborn underwent postnatal resection of a CPAM Type II and is doing well. We hypothesize that fetal tracheobronchoscopy provided the following potential diagnostic and therapeutic benefits: (1) exclusion of an obstructive bronchial lesion; (2) disimpaction of bronchial debris from the saline lavage that we posit may have contributed to the rapid reduction in CPAM size.