Irreversible Asthma Research Articles

Endobronchial biopsy in the final diagnosis of chronic obstructive pulmonary disease and asthma: a clinicopathological study.

BACKGROUNDAsthma and chronic obstructive pulmonary disease (COPD) are chronic conditions with an increasing prevalence in developing countries. The evaluation of endobronchial biopsies has emerged as a tool to differentiate between both conditions via the measurement of the reticular basement membrane (RBM) thickness with various conclusions drawn from different studies.OBJECTIVESCompare the thickness of the RBM between asthma and COPD and evaluate other histomorphological features in both groups.DESIGNProspective, descriptive and analytical.SETTINGUniversity teaching hospital.PATIENTS AND METHODSThe study included patients with COPD and irreversible and reversible asthma with diagnosis based on clinical assessment, pulmonary function tests and high-resolution computed tomography scans. Endobronchial biopsies were obtained from all patients and, using a light microscope and a computerized image analyzer, the thickness of the reticular basement membrane was calculated in all patients. We also made a qualitative assessment of other histomorphological features.MAIN OUTCOME MEASURESMean RBM thickness.SAMPLE SIZEThirty male patients.RESULTSThe mean RBM thickness in asthmatic patients was 8.9 (2.4) μm. The mean RBM thickness in COPD patients was 5.3 (1.1) μm. However, there was no thickening of the RBM in patients with reversible asthma. The RBM was significantly thicker in patients with irreversible asthma than in patients with COPD or reversible asthma. There were no significant differences in epithelial desquamation or metaplasia, mucosal or submucosal inflammation, the presence of eosinophils, submucosal glandular hyperplasia or submucosal smooth muscle hyperplasia between groups.CONCLUSIONSThe thickness of the RBM is the only reproducible histopathological feature to differentiate COPD from irreversible asthma.LIMITATIONSThe study included a limited number of patients. A qualitative approach was used to compare epithelial cell injury, inflammation, submucosal glandular and muscular hyperplasia.

Can computed tomography and carbon monoxide transfer coefficient diagnose an asthma‐like phenotype in COPD?

Post-mortem and computed tomography (CT) studies indicated that emphysema is a feature of COPD even in the 'blue bloater/chronic bronchitis' type. We aim to test the hypothesis that the non-emphysematous patients are distinct from the main body of COPD and are more akin to asthmatic patients. We studied 54 patients with COPD. Emphysema was measured by Goddard's visual scoring of CT scan and the carbon monoxide transfer coefficient (KCO). Bronchial biopsy was offered for thickness of basement membrane (BM) (≥7 µm) as a marker of remodelling in irreversible asthma. Spirometry was repeated after therapy with Budesonide/Formoterol for 1 year. The non-emphysematous phenotype were 24 of 54 patients (44%) by CT scan and 23 of 54 patients (43%) by KCO, showing agreement in 53 out of 54 patients. The non-emphysematous patients were younger, had higher forced expiratory volume in 1 s (FEV1 ) (median 61% vs 49.7%), greater prevalence of hypertrophy of nasal turbinates and higher serum IgE. The emphysematous phenotype had lower BMI and greater dyspnoea score. The BM was thickened in 11 of 14 and 0 of 10 patients in the non-emphysematous and emphysematous groups, respectively. Three patients without emphysema and a normal BM normalized their FEV1 upon receiving inhaled corticosteroid (ICS)/long-acting β2 agonist (LABA). All the non-emphysematous improved their FEV1 after ICS/LABA (median = 215 mL). The median decline in the emphysematous was -65 mL. The non-emphysematous phenotype of COPD displays important features of asthma: clinical picture, histology and response to ICS. CT and KCO can predict spirometric response to ICS/LABA.

Re: Phenotyping of chronic obstructive pulmonary disease: heterogeneity and its clinical relevance

We read the above article (published in Curr Respir Care Rep 2012 1:189–198) with great interest, and would like to make the following comments. The review very correctly refers to the great potential of targeting therapy to specific COPD phenotypes, and indeed cites several valuable examples of targeted therapy. However, there is no mention of the two most important of these phenotypes, namely irreversible asthma and eosinophilic COPD. Approximately 35 % of COPD patients suffer from irreversible asthma, as evidenced by bronchial histology, normal carbon monoxide diffusion capacity, absence of emphysema on CT scan, strong association with allergic rhinitis, and responsiveness to prednisolone or inhaled corticosteroids (ICS) [1–3]. Eosinophilic COPD, defined by sputum eosinophilia of more than 3 %, is reported for 20– 40 % of COPD patients. Apart from these two phenotypes, cases of COPD are not steroid-responsive [4–7]. Identifying these two groups would result in more effective and less expensive therapy. The review defined the “overlap syndrome” (of asthma and COPD) as the presence of increased variability of airflow in a COPD patient. There is no agreement on a definition of the “syndrome” because workers have used a variety of other criteria to diagnose it, including the patient reporting having received an asthma diagnosis (with or without age limitation) [8], or the presence of “asthmatic symptoms” including cough, episodic chest tightness or wheezing in a patient with COPD [9, 10]. Sputum eosinophilia or atopy have also been used as criteria for diagnosis [11, 12]. In therapeutic trials the response of the “overlap syndrome” to ICS was not uniform, but was related to the presence of sputum eosinophila [9]. This further demonstrates the heterogeneity of the “overlap syndrome” and the difficulty of accepting its existence as a distinct, definable entity or phenotype. The condition has been called a “nonsyndrome” because of its arbitrary definitions on which there is no agreement, its inability to be defined by objective criteria, for example histology or CT scan, and its lack of uniform response to ICS [13]. More seriously, accepting the existence of an overlap syndrome could adversely affect phenotyping and its objective of separating the different strands of COPD.

A challenge to the seven widely believed concepts of COPD.

This review proposes a critical reassessment (based entirely on published evidence) of the following seven common beliefs about chronic obstructive pulmonary disease (COPD): (1) COPD is one disease. (2) There is a valid definition for COPD. (The current definition includes cases of irreversible asthma and bronchiectasis, and occasionally, other obstructive lung conditions). (3) Irreversible asthma in smokers and COPD cannot be differentiated. (4) A "chronic bronchitis" form of COPD exists and is characterized by blue bloater status and normal carbon monoxide diffusion studies. (5) Phenotyping has no bearing on medication choice in COPD. (6) Computerized scoring of lung attenuation on CT scans can diagnose emphysema. (Emphysema scores overlap in irreversible asthma and COPD); however, qualitative visual changes may be useful for differentiation. (7) A definable entity called the overlap (of COPD and asthma) syndrome exists. Conflict over the above-mentioned points denies patients proper phenotype-guided therapy and encourages a multidrug approach to COPD management. The recently coined term, overlap syndrome, invites a double-barreled therapy aimed at asthma and COPD, despite the absence of any agreement about how to define the syndrome and the lack of any related drug trials (in the area of inhaled corticosteroids). A diagnosis of COPD is associated with high morbidity and escalating costs, suggesting the need for a thorough new examination of the evidence.

Abrupt withdrawal of inhaled corticosteroids does not result in spirometric deterioration in chronic obstructive pulmonary disease: Effect of phenotyping?

BACKGROUND AND OBJECTIVE:Some studies show a decline of FEV1 only one month after withdrawal of inhaled corticosteroids (ICS), while others show no decline. We speculate that the presence of an asthma phenotype in the Chronic Obstructive Pulmonary Disease (COPD) population, and that its exclusion may result in no spirometric deterioration.METHODS:We performed a prospective clinical observation study on 32 patients who fulfilled the Global Initiative for Chronic Obstructive lung disease definition of COPD (Grade II-IV). They were divided into two phenotypic groups. 1. Irreversible asthma (A and B) (n = 13): A. Asthma: Bronchial biopsy shows diffuse thickening of basement membrane (≥ 6.6 μm). B. Airflow limitation (AFL) likely to be asthma: KCO > 80% predicted if the patient refused biopsy. 2. COPD (A and B) (n = 19): A. COPD: hypercapneic respiratory failure with raised bicarbonate, panlobular emphysema with multiple bullas, or bronchial biopsy showing squamous metaplasia and epithelial/subepithelial inflammation without thickening of the basement membrane. B. AFL likely to be COPD: KCO < 80% predicted.RESULTS:The asthma phenotype was significantly younger, had a strong association with hypertrophy of nasal turbinates, and registered a significant improvement of FEV1 (350 ml) vs a decline of - 26.5 ml in the COPD phenotype following therapy with budesonide/formoterol for one year. Withdrawal of budesonide for 4 weeks in the COPD phenotype resulted in FEV1 + 1.33% (SD ± 5.71) and FVC + 1.24% (SD ± 5.32); a change of <12% in all patients.CONCLUSIONS:We recorded no spirometric deterioration after exclusion of the asthma phenotype from a COPD group.

Exhaled breath 8-isoprostane as a marker of asthma severity.

IntroductionOxidative stress is a non-specific feature of airway inflammation in asthmatics. 8-Isoprostane (8-IP), a prostaglandin-F2α isomer, is a relatively new marker of oxidative stress and may be measured in exhaled breath condensate (EBC) of patients with asthma. This research study aimed to evaluate the usefulness of EBC 8-IP as a marker of severity and control of severe adult asthma.Material and methodsTwenty-seven severe, never-smoking asthmatics were studied. According to positive or negative reversibility testing, this group was subdivided into reversible and irreversible asthma groups. All participants were observed for 8 weeks during which they completed daily diary observations including day and night symptoms, number of awakenings, peak expiratory flow (PEF) variability, daily rescue medication usage and oral steroids consumption. They attended the clinic 3 times and on these occasions spirometry assessments, EBC collection and asthma control tests (ACT) were done. Two control groups were included: 11 healthy never-smokers and 16 newly diagnosed and never-treated, non-smoking mild asthmatics.ResultsThere were no statistically significant differences between severe asthma and healthy control or never-treated asthma groups in concentrations of EBC 8-IP (median and interquartile range: 4.67; 2.50-27.92 vs. 6.93; 2.5-12.98 vs. 3.80; 2.50-10.73, respectively). No correlations were found between EBC 8-IP and asthma control parameters, such as ACT results, night and day symptoms, consumption of rescue medication, percentage of days free of oral steroids, PEF diurnal variation, lung function test results, forced expiratory volume in the 1 s reversibility, and markers of systemic inflammation.ConclusionsOur study results suggest that EBC 8-IP measurements are not useful for asthma monitoring.

Identification of patients with irreversible asthma

Rationale To define and report a series of 13 patients with the syndrome of irreversible asthma, their clinical characteristics, specific radiological findings, pulmonary function tests, response to appropriate therapy and long term outcomes. Methods Retrospective analysis of patients with severe asthma in a university-based Allergy/Immunology service with a large population of corticosteroid-dependent patients with asthma. Results The age of patients ranged from 43 to 85 years, with a mean duration of asthma of 45.9 years (SD=13.2 years) and 11 of the 13 patients (84.6%) had been hospitalized at least once in their life for asthma. No patient had evidence of any other pulmonary disease processes. Eleven of thirteen patients (84.6%) had positive skin tests to at least one aeroallergen and 6/11 patients (54.5%) had a history of receiving at least 3 years of immunotherapy. The mean duration of daily or alternate-day oral corticosteroid treatment was 17.8 years (SD=9.4 years). All patients had an average FEV1% of 51.6% (SD=12.8) at presentation. Despite intensive pharmacotherapy with continuous systemic corticosteroids and inhaled corticosteroids, 4 of the 13 patients (30.8%) demonstrated an accelerated decline in FEV1 (>50 mL/yr). Conclusions We have described a series of 13 patients with long standing asthma who demonstrate irreversible airway obstruction despite long-term systemic and inhaled corticosteroids. Irreversible asthma might be applied to these patients in whom fixed obstruction has occurred in the absence of other pulmonary diseases and despite intensive treatment.

Airways Obstruction in Patients With Long-term Asthma Consistent With Irreversible Asthma'

To describe a series of eight patients with long-term asthma and pulmonary function consistent with "end-stage," irreversible obstruction. Retrospective descriptive analysis of patients with severe asthma. A university-based allergy-immunology service with a large population of corticosteroid-dependent patients with asthma. Eight patients with long-standing asthma and apparently irreversible airways obstruction despite long-term oral and inhaled corticosteroid therapy. Pulmonary function data, radiographic studies including chest radiograph and high-resolution CT of the chest, and serologic analysis to rule out allergic bronchopulmonary aspergillosis and alpha1-antitrypsin deficiency had been performed as indicated, and these results were obtained through chart review. The age of the patients ranged from 41 to 58 years, with a mean duration of asthma of 39 years (SD = 12.4 years). No patient had evidence of any other pulmonary disease process. The mean duration of daily or alternate-day oral corticosteroid treatment was 15.8 years (SD=11.8 years). Despite intensive pharmacotherapy, all patients had an FEV1 57% (42+/-12%) with marked small airways disease as reflected in the forced expiratory flow between 25% and 75% of the FVC. Three of the eight patients demonstrated an accelerated decline in FEV1 despite continuous systemic corticosteroids. We have described a series of eight patients with long-standing asthma who demonstrate irreversible airways obstruction despite long-term systemic and inhaled corticosteroids. The term "end-stage asthma" or irreversible asthma might be applied to these patients in whom fixed obstruction has occurred in the absence of other pulmonary diseases.

625 Irreversible asthma is an indication for high resolution chest computed tomography (HRCCT)

625 Irreversible asthma is an indication for high resolution chest computed tomography (HRCCT)