Fixed Airway Obstruction Research Articles

Respiratory Disease Among Flavoring-exposed Workers in Food and Flavoring Manufacture

Fixed airways obstruction was found in workers producing microwave popcorn in relation to inhaling synthetic butter flavoring volatiles in 2000. Since then, an industry-wide hazard of clinical bronchiolitis obliterans was found in other microwave-popcorn plants, in flavoring manufacture, and in diac

Regulator of G-Protein Signaling–5 Inhibits Bronchial Smooth Muscle Contraction in Severe Asthma

Severe asthma is associated with fixed airway obstruction attributable to inflammation, copious luminal mucus, and increased airway smooth muscle (ASM) mass. Paradoxically, studies demonstrated that the hypertrophic and hyperplastic ASM characteristic of severe asthma has reduced contractile capacity. We compared the G-protein-coupled receptor (GPCR)-induced Ca(2+) mobilization and expression of GPCRs and signaling proteins related to procontractile signaling in ASM derived postmortem from subjects who died of nonrespiratory causes, with cells from subjects who died of asthma. Despite the increased or comparable expression of contraction-promoting GPCRs (bradykinin B2 or histamine H1 and protease-activated receptor 1, respectively) in asthmatic ASM cells relative to cells from healthy donors, asthmatic ASM cells exhibited reduced histamine-induced Ca(2+) mobilization and comparable responses to bradykinin and thrombin, suggesting a postreceptor signaling defect. Accordingly, the expression of regulator of G-protein signaling-5 (RGS5), an inhibitor of ASM contraction, was increased in cultured, asthmatic ASM cells and in bronchial smooth muscle bundles of both human subjects with asthma and allergen-challenged mice, relative to those of healthy human subjects or naive mice. The overexpression of RGS5 impaired the release of Ca(2+) to thrombin, histamine, and carbachol, and reduced the contraction of precision-cut lung slices to carbachol. These results suggest that increased RGS5 expression contributes to decreased myocyte shortening in severe and fatal asthma.

An RGS4-Mediated Phenotypic Switch of Bronchial Smooth Muscle Cells Promotes Fixed Airway Obstruction in Asthma

In severe asthma, bronchodilator- and steroid-insensitive airflow obstruction develops through unknown mechanisms characterized by increased lung airway smooth muscle (ASM) mass and stiffness. We explored the role of a Regulator of G-protein Signaling protein (RGS4) in the ASM hyperplasia and reduced contractile capacity characteristic of advanced asthma. Using immunocytochemical staining, ASM expression of RGS4 was determined in endobronchial biopsies from healthy subjects and those from subjects with mild, moderate and severe asthma. Cell proliferation assays, agonist-induced calcium mobilization and bronchoconstriction were determined in cultured human ASM cells and in human precision cut lung slices. Using gain- and loss-of-function approaches, the precise role of RGS proteins was determined in stimulating human ASM proliferation and inhibiting bronchoconstriction. RGS4 expression was restricted to a subpopulation of ASM and was specifically upregulated by mitogens, which induced a hyperproliferative and hypocontractile ASM phenotype similar to that observed in recalcitrant asthma. RGS4 expression was markedly increased in bronchial smooth muscle of patients with severe asthma, and expression correlated significantly with reduced pulmonary function. Whereas RGS4 inhibited G protein-coupled receptor (GPCR)-mediated bronchoconstriction, unexpectedly RGS4 was required for PDGF-induced proliferation and sustained activation of PI3K, a mitogenic signaling molecule that regulates ASM proliferation. These studies indicate that increased RGS4 expression promotes a phenotypic switch of ASM, evoking irreversible airway obstruction in subjects with severe asthma.

Dysfunctional breathing phenotype in adults with asthma ‐ incidence and risk factors

BackgroundAbnormal breathing patterns may cause characteristic symptoms and impair quality of life. In a cross-sectional survey 29% of adults treated for asthma in primary care had symptoms suggestive of dysfunctional breathing (DB), more likely to be female and younger, with no differences for severity of asthma. No clear risk factors were demonstrated for DB in asthma, nor the impact of asthma medication was evaluated. The objective of this study was to describe the DB phenotype in adults with asthma treated in a specialised asthma centre.MethodsAdult patients aged 17–65 with diagnosed asthma were screened for DB using the Nijmegen questionnaire (positive predictive score >23) and confirmed by progressive exercise testing. The following were evaluated as independent risk factors for DB in the multiple regression analysis: female sex; atopy, obesity, active smoker, moderate/severe rhinitis, psychopathology, GERD, arterial hypertension; severe asthma, asthma duration > 5 years, lack of asthma control, fixed airway obstruction, fast lung function decline, frequent exacerbator and brittle asthma phenotypes; lack of ICS, use of LABA or LTRA.Results91 adults with asthma, mean age 35.04 ±1.19 years, 47(51.65%) females were evaluated. 27 (29.67%) subjects had a positive screening score on Nijmegen questionnaire and 16(17.58%) were confirmed by progressive exercise testing as having DB. Independent risk factors for DB were psychopathology (p = 0.000002), frequent exacerbator asthma phenotype (p = 0.01) and uncontrolled asthma (p < 0.000001).ConclusionDysfunctional breathing is not infrequent in asthma patients and should be evaluated in asthma patients presenting with psychopathology, frequent severe asthma exacerbations or uncontrolled asthma. Asthma medication (ICS, LABA or LTRA) had no significant relation with dysfunctional breathing.

Clinical Course of Eosinophilic Bronchitis in Children

Purpose:It has been identified that eosinophilic bronchitis (EB) in adults can progress to asthma or fixed airway obstruction. In the present study, we evaluated the clinical course and prognosis of EB in children and their relationship with accompanying rhinosinusitis. Methods:A total of 55 children with EB followed up for over than a year after the diagnosis were enrolled for the present study. We classified the subjects into two groups according to the prognosis and the presence of rhinosinusitis, respectively, and compared them with respect to clini- cal characteristics, eosinophil percentage in induced sputum, fractional exhaled nitric oxide (FeNO) and pulmonary function test. The poor prognostic group was defined as the children with asthma or asthma-like symptoms, or persistent or recurrent chronic cough in the long-term follow-up. Results:The poor prognosis was achieved in 12 children (22%), and 3 children (5%) amongst them were diagnosed with asthma. There were no significant differences in clinical characteristics, eosinophil percentages in induced sputum, FeNO, spirometry and IOS according to the prognosis and the presence of rhinosinusitis. Additionally, the children with rhinosinusitis did not show any poorer outcome than those without rhinosinusitis. Conclusion:There were some limitations of this study for which the relationship between EB and rhinosinusitis in children was evaluated. However, in case of either poor short-term response to inhaled corticosteroids or elevated eosinophilic inflammation in airways or abnormal airway reversibility in impulse oscillometry, the long-term prognosis of EB in children needs to be consi- dered, regardless of the presence of rhinosinusitis. (Pediatr Allergy Respir Dis(Korea) 2012;22: 273-281)

Smoking, longer disease duration and absence of rhinosinusitis are related to fixed airway obstruction in Koreans with severe asthma: findings from the COREA study

BackgroundThe clinical manifestations of severe asthma are heterogeneous. Some individuals with severe asthma develop irreversible fixed airway obstruction, which is associated with poor outcomes. We therefore investigated the factors associated with fixed airway obstruction in Korean patients with severe asthma.MethodsSevere asthma patients from a Korean adult asthma cohort were divided into two groups according to the results of serial pulmonary function tests. One group had fixed airway obstruction (FAO) [forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) ratio < 0.7, n = 119] and the other had reversible airway obstruction (RAO) [FEV1/FVC ratio ≥ 0.7, n = 116]. Clinical and demographic parameters were compared between the two groups.ResultsMultivariate analysis showed that longer duration of disease, greater amount of cigarette smoking and absence of rhinosinusitis were significantly related to the development of FAO in severe asthmatics. Other parameters, including atopic status, pattern of airway inflammatory cells in induced sputum, and frequency of asthma exacerbations did not differ between the FAO and RAO groups.ConclusionSevere asthma patients with longer disease duration and the absence of rhinosinusitis are more likely to develop FAO. This study also demonstrates the importance of quitting smoking in order to prevent irreversible airway obstruction. Further investigation is required to determine the mechanism by which these factors can modify the disease course in Korean patients with severe asthma.

External validation of exhaled breath profiling using an electronic nose in the discrimination of asthma with fixed airways obstruction and chronic obstructive pulmonary disease

Fixed airflow limitation can be found both in asthma and chronic obstructive pulmonary disease (COPD), posing a day-to-day diagnostic challenge. We aimed to determine the external validity of metabolomic analysis of exhaled air by electronic nose for distinguishing asthma and COPD in patients with fixed airways obstruction. One hundred patients were included in a cross-sectional design: 60 asthma patients: 21 with fixed airways obstruction (fixed asthma), 39 with reversible airways obstruction (classic asthma) and 40 COPD patients (GOLD stages II-III). Standardized sampling of exhaled breath was performed and volatile organic compounds were captured using an electronic nose resulting in breathprints. External validity in newly recruited patients (validation sets) was tested using a previous and independent training set. Breathprints were analysed by principal component and canonical discriminant analysis and area under the curve (AUC) of receiver operating characteristic curves. External validity of breathprints showed 88% accuracy for distinguishing fixed asthma from COPD (AUC 0.95, 95% CI 0.84-1.00, sensitivity 85%, specificity 90%) and 83% for classic asthma (AUC 0.93, 95% CI 0.87-1.00, sensitivity 91%, specificity 90%) (both P<0.001). Discriminative accuracy was not confounded by current smoking. External validation of exhaled breath molecular profiling shows high accuracy in distinguishing asthma and COPD in newly recruited patients with fixed airways obstruction. Exhaled air analysis may therefore reduce misdiagnosis in obstructive airways diseases, potentially leading to more appropriate management.

Physical Forces and Airway Remodeling in Asthma

Asthma is a disease of the airways characterized by variable airflow obstruction, bronchial hyperresponsiveness, and airway inflammation. Asthma is also accompanied by changes to the structure and composition of the airway walls, collectively termed airway remodeling.1 Cardinal features of airway remodeling include increased numbers of mucus-secreting epithelial cells, thickening of the subepithelial collagen layer, and increases in vascularity and smooth-muscle mass around the airways. There is a strong consensus that airway remodeling contributes to the decline in lung function and the development of fixed airway obstruction present in patients with chronic, persistent asthma.2 Evidence indicates that aspects of airway remodeling . . .

Reduced apoptosis of CD8+ T-Lymphocytes in the airways of smokers with mild/moderate COPD

Chronic obstructive pulmonary disease (COPD) is characterised by chronic inflammation in airways and lung parenchyma. CD8+ T-lymphocytes, crucial effector and regulatory cells in inflammation, are increased in the central and peripheral airways in COPD. The aim of this study was to assess the role of apoptosis in the accumulation of CD8+ T-lymphocytes within the airway wall in COPD. We examined the submucosa of transverse sections of central and peripheral airways from post-operative tissues from non-smokers (n=16), smokers with normal lung function (n=16), smokers with mild/moderate COPD (n=16), and smokers with severe/very severe COPD (n=9). TUNEL and immunohistochemistry techniques were used to identify apoptosis and cell phenotype, respectively. The percentage of apoptotic CD8+ T-lymphocytes was significantly lower (p<0.0001) in smokers with mild/moderate COPD than in non-smokers, smokers with normal lung function, and smokers with severe/very severe COPD, and was positively related to values of FEV(1) and FEV(1)/FVC ratio, both in central and in peripheral airways. These data suggest that reduced apoptosis of CD8+ T-lymphocytes may be an important mechanism that contributes to the accumulation of these cells in the airway submucosa in smokers with mild/moderate COPD.

Protective effects of basic fibroblast growth factor in the development of emphysema induced by interferon-γ

Recent clinical evidence indicates that the non-eosinophilic subtype of severe asthma is characterized by fixed airway obstruction, which may be related to emphysema. Transgenic studies have demonstrated that high levels of IFN-γ in the airways induce emphysema. Fibroblast growth factor 2 (FGF2), which is the downstream mediator of TGF-β, is important in wound healing. We investigated the role of FGF2 in IFN-γ-induced emphysema and the therapeutic effects of recombinant FGF2 in the prevention of emphysema in a severe non-eosinophilic asthma model. To evaluate the role of FGF2 in IFN-γ-induced emphysema, lung targeted IFN-γ transgenic mice were cross-bred with FGF2-deficient mice. A severe non-eosinophilic asthma model was generated by airway application of LPS-containing allergens twice a week for 4 weeks. To evaluate protective effects of FGF2, recombinant FGF2 (10 μg) was injected subcutaneously during allergen challenge in the severe asthma model. We found that non-eosinophilic inflammation and emphysema induced by transgenic overexpression of IFN-γ in the airways were aggravated by the absence of FGF2. Airway challenge with LPS-containing allergens induced more inflammation in mice sensitized with LPS-containing allergens compared to challenge with allergens alone. In addition, LPS-induced lung inflammation and emphysema depended on IFN-γ but not on IL-13. Interestingly, emphysema in the severe asthma model was significantly inhibited by treatment with recombinant FGF2 during allergen challenge, whereas lung inflammation was unaffected. Therefore, our present data suggest that FGF2 may help protect against IFN-γ-induced emphysema, and that recombinant FGF2 may help lessen the severity of emphysema.

Industry‐wide medical surveillance of California flavor manufacturing workers: Cross‐sectional results

Two cases of bronchiolitis obliterans in flavor manufacturing workers prompted California health and labor agencies to initiate industry-wide surveillance. Companies' physicians submitted cross-sectional questionnaire and spirometry data for 467 workers in 16 workplaces. We compared prevalence ratios of respiratory symptoms, diagnoses, and abnormal spirometry to a general population sample. We calculated odds ratios for risk factors for spirometric obstructive abnormality. Flavoring workers were 2.7 times more likely than the general population to have severe airways obstruction. Risk factors identified for 18 cases with obstruction from six companies included younger age, Hispanic ethnicity, liquid and powder production work, greater company diacetyl usage, and having a coworker with obstruction. Severity of obstruction was related to tenure. At least 12 workers had probable occupational fixed airways obstruction. The flavoring industry risk of severe lung disease justifies lowering flavoring exposures and medical screening for secondary prevention until worker safety is demonstrated.

Improvements in Symptoms and Quality of Life following Exercise Training in Older Adults with Moderate/Severe Persistent Asthma

Background: Some individuals with moderate/severe persistent asthma develop irreversible airway obstruction. These individuals present with dyspnoea, exercise intolerance and impaired quality of life (QOL), all of which could potentially be alleviated with exercise training. Objective: To investigate whether exercise training improves functional exercise capacity and QOL in middle-aged and older adults with fixed airway obstruction asthma (FAOA). Methods: 35 subjects aged 67.8 ± 10.6 years, with FEV₁ 59 ± 16% of predicted, were randomised to a 6-week ‘intervention’ period of supervised exercise training (n = 20) or usual care (n = 15). This period was preceded by a 3-week run-in period during which asthma control was assessed weekly. Functional exercise capacity (6-min walk distance, 6MWD) and QOL (Asthma QOL Questionnaire, AQLQ) were measured before, immediately following and 3 months after the intervention period. Results: 34 subjects (exercise group, n = 19, and control group, n = 15) completed the intervention period. Relative to the control group, the exercise group had greater improvements immediately following and 3 months after the intervention in the AQLQ symptom domain (0.61, p = 0.001, and 0.57 points per item, p = 0.005) and AQLQ activity limitation domain (0.43, p = 0.04, and 0.55 points per item, p = 0.04). 6MWD increased (36 ± 37 m, p < 0.01) in the exercise group immediately following training and remained elevated (34 ± 45 m, p < 0.01) at the 3-month follow-up. The magnitude of change in 6MWD between groups was not significant, despite no change in the control group. Conclusions: Supervised exercise training improves symptoms and QOL in adults with FAOA.

Asthmatics Without Rhinitis Have More Fixed Airway Obstruction Than Those With Concurrent Rhinitis

PurposeRhinitis and asthma usually occur together. There are increasing evidences that allergic rhinitis (AR) may influence the clinical course of asthma. The aim of this study is to evaluate clinical parameters and therapeutic response in patients with between asthma and asthma with AR.MethodsFour-hundred eighty-five patients with asthma and 428 asthmatics with AR, who had lesser than 50 years old and smoked less than 10 pack-years were recruited. We compared FEV1 and FEV1/FVC following bronchodilator, atopy, IgE, emphysema on HRCT, and aspirin intolerance between two groups. Also we compared physiologic fixed airway obstruction defined using FEV1/FVC and FEV1 less than 75% following anti-asthmatic drug for 1 year.Results46.8% (428/913) asthmatics suffered from AR. There were no differences of total IgE, body mass index, PC20, sputum eosinophils and emphysema on HRCT between two groups. The age in asthmatics was higher than that in those with AR. FEV1/FVC was lower in asthmatics than in those with AR. The prevalence of atopy was higher in asthmatics with AR than in asthmatics. Aspirin intolerance was higher in asthmatics with AR than in asthmatics (42/218 vs 13/109, P=0.001). Fixed airway obstruction were more observed in asthmatics than in those with AR (39/319 vs 28/355, P=0.001) after anti-asthmatic drug for 1 year.ConclusionsAsthmatics with AR had more atopy and aspirin intolerance than asthmatics, and asthmatics had poor response to anti-inflammatory drugs than those with concurrent rhinitis, indicating that asthmatics have more fixed airway obstruction than those with concurrent rhinitis.

Overlap Between Asthma and COPD: Where the Two Diseases Converge

Asthma and chronic obstructive pulmonary disease (COPD) are traditionally recognized as distinct diseases, with some clearly separate characteristic. Asthma originates in childhood, is associated with allergies and eosinophils, and is best treated by targeting inflammation, whereas COPD occurs in adults who smoke, involves neutrophils, and is best treated with bronchodilators and the removal of risk factors. However, the distinction between the two is not always clear. Patients with severe asthma may present with fixed airway obstruction, and patients with COPD may have hyperresponsiveness and eosinophilia. Recognizing and understanding these overlapping features may offer new insight into the mechanisms and treatment of chronic airway inflammatory diseases.

Clinical prediction rule to diagnose post‐infectious bronchiolitis obliterans in children

Infant pulmonary function testing has a great value in the diagnosis of post-infectious bronchiolitis obliterans (BOs), because of characteristic patterns of severe and fixed airway obstruction. Unfortunately, infant pulmonary function testing is not available in most pediatric pulmonary centers. To develop and validate a clinical prediction rule (BO-Score) to diagnose children under 2 years of age with BOs, using multiple objectively measured parameters readily available in most medical centers. Study subjects, children under 2 years old with a chronic pulmonary disease assisted at R. Gutierrez Children's Hospital of Buenos Aires. Patients were randomly divided into a derivation (66%) and a validation (34%) set. ROC analyses and multivariable logistic regression included significant clinical, radiological, and laboratory predictors. The main outcome measure was a diagnosis of BOs. The performance of the BO-Score was tested on the validation set. Hundred twenty-five patients were included, 83 in the derivation set and 42 in the validation set. The BO-Score (area under ROC curve = 0.96; 95% CI, 0.9-1.0%) was developed by assigning points to the following variables: typical clinical history (four points), adenovirus infection (three points), and high-resolution computed tomography with mosaic perfusion (four points). A Score > or =7 predicted the diagnosis of BOs with a specificity of 100% (95% CI, 79-100%) and a sensitivity of 67% (95% CI, 47-80%). The BO-Score is a simple-to-use clinical prediction rule, based on variables that are readily available. A BO-Score of 7 or more predicts a diagnosis of post-infectious BOs with high accuracy.

Airway Stenosis-Related Increase of Pulmonary Pressure During High-Frequency Jet Ventilation Depends on Injector’s Position

High-frequency jet ventilation (HFJV) can lead to high-airway pressures under certain conditions. In this laboratory study, we evaluated the influence of the injector's position relative to a fixed airway obstruction on peak pressures in a tracheal-lung model. We administered HFJV via a metal jet injector at varying distances from connectors simulating laryngotracheal airway stenosis. Peak pressures were measured inside the lung model. When the jet nozzle was near the simulated stenosis, peak pressure within the test lung increased and reached a maximum when the stenosis' lumen decreased despite unchanged parameters of jet gas flow. With the injector's tip placed 8-10 cm in front of the stenosis, reduction of airway diameter did not result in an increase of distal peak pressures. These observations were similar for all settings of gas flow (0.5-1.5 bar driving pressure) and frequencies. This study in a lung model suggests that placing an injector more than 8 cm proximal to a laryngotracheal stenosis will prevent changes in intrapulmonary pressure related to the degree of stenosis or driving pressure during HFJV. The location of the injector chosen for clinical care should balance the need for effective ventilation with the risk of barotrauma.

Evaluation of airway hyperresponsiveness and exhaled nitric oxide as risk factors for airway remodeling in patients with stable asthma

Chronic eosinophilic airway inflammation, airflow limitation, and airway hyperresponsiveness (AHR) are distinctive features of bronchial asthma. Exhaled nitric oxide (eNO) is a marker of eosinophilic airway inflammation. Airway remodeling due to chronic airway inflammation results in fixed airway obstruction. Asthmatic patients have been reported to have greater declines in forced expiratory volume in 1 second (FEV(1)) over time than nonasthmatic patients. This longitudinal observational study aimed to elucidate outcomes and risk factors for the decline in FEV(1) in patients with stable asthma. Postbronchodilator FEV(1) was measured in 30 outpatients with stable asthma every 6 months for 5 years. We calculated the rate of decline in postbronchodilator FEV(1) (deltaFEV(1)/year) in each subject and adjusted deltaFEV(1)/year with predictive FEV(1). Patients were examined while their asthma was well controlled. In the first observation period, we measured AHR to methacholine (the provocative concentration of methacholine causing a 20% fall in FEV(1) [PC(20)]). In the second observation period (defined as the period over 2 years from start of observation), we measured methacholine PC(20) and eNO. The mean deltaFEV(1)/year (SEM) was -36 +/- 4 mL/year and the adjusted deltaFEV(1)/year (SEM) was -0.015 +/- 0.001/year. Adjusted deltaFEV(1)/year did not correlate with eNO measured during the second observation period or methacholine PC(20) measured during the first observation period. On the other hand, methacholine PC(20) measured during the latter period was correlated significantly with adjusted deltaFEV(1)/year. Persistent AHR may be a risk factor for longitudinal decline in FEV(1) in asthma patients even if their asthma is stable and well controlled by inhaled corticosteroid.

Role of Relaxin in Regulation of Fibrosis in the Lung

Airway remodeling changes are a key pathological feature of asthma. They are associated with airway hyperresponsiveness and fixed airway obstruction. Aged, relaxin-deficient mice display structural changes resembling airway remodeling in asthma, including thickening of the bronchial epithelium and extracellular matrix (ECM) deposition in the subepithelial region. Relaxin-deficient mice also have exaggerated airway remodeling in models of allergic airway disease compared to wild-type controls. Both in vitro and in vivo studies have suggested that airway fibrosis may drive other changes of airway remodeling, including epithelial changes. A suggested paradigm is that subepithelial fibrosis (deposition of ECM in the basement membrane region) may lead to increased epithelial cell proliferation and transforming growth factor-beta1 production, which in turn may lead to further fibrosis. Relaxin may therefore prevent or reverse activation of the epithelial and fibroblast remodeling in asthma. Control of epithelial remodeling and ECM production in the airway wall may play an important role in maintaining normal lung function. Understanding how relaxin protects against airway remodeling changes may have important implications in developing new therapies to treat airway remodeling in asthma.

The Impact of Smoking on Clinical and Therapeutic Effects in Asthmatics

Smoking is associated with poor symptom control and impaired therapeutic responses in asthma. A total of 843 patients with asthma were recruited. The patients received treatment for 1 yr according to the severity of their asthma. We compared the forced expiratory volume in 1 sec (FEV1), the ratio of FEV1 to forced vital capaity (FVC), atopy, total IgE, emphysema on high-resolution computed tomography (HRCT), the number of near-fatal asthma attacks, and physiological fixed airway obstruction between the smoking and nonsmoking groups. The study population consisted of 159 (18.8%) current smokers, 157 (18.7%) ex-smokers, and 525 (62.5%) nonsmokers. Although the prevalence of atopy was not different between the smoking and nonsmoking groups, the total IgE was higher among the smokers than the nonsmokers. Compared with the nonsmoking group, the smokers had a lower FEV1 % predicted and forced expiratory flow between 25 and 75% of FVC. A greater prevalence of emphysema and a significantly higher number of asthmatic patients with fixed airway obstruction were detected in the smoking versus nonsmoking group. The 37.5% of asthmatic patients who were former or current smokers showed decreased pulmonary function and increased IgE, emphysema on HRCT, and fixed airway obstruction, indicating that smoking can modulate the clinical and therapeutic responses in asthma.

Tiotropium bromide is effective for severe asthma with noneosinophilic phenotype

To the Editor: Although currently available asthma medications are very effective in the majority of cases, there remains a subgroup for which disease control is difficult. Anticholinergics have long been used to treat asthma, although their current role in therapy is supplementary 1. Tiotropium bromide, a recently developed anticholinergic, is a long-acting bronchodilator with a well-established effectiveness for treating chronic obstructive pulmonary disease 2. Although some subgroups of asthmatics seem to respond better to anticholinergics, the pathophysiological features of these responders have yet to be established 3, 4. Previous studies that aimed to identify asthma subgroups which respond better to anticholinergics have suggested the following clinical features: patients with nocturnal symptoms, chronic asthma showing concurrent fixed airway obstruction, intrinsic asthma with longer duration of disease and nonatopic asthma 1, 5. The objective of the present study was to determine the characteristics of asthmatics which show good responses to tiotropium bromide. We investigated the efficacy of tiotropium bromide in …