Reversible Airflow Obstruction Research Articles

Role of GM-CSF and IRF5 in steroid refractory asthma (P6247)

Abstract Asthma is a heterogeneous, inflammatory disease of the airways characterized by reversible airflow obstruction and bronchoconstriction. 10% of asthma patients are categorized as severe asthmatics (SA), showing mixed neutrophilic/eosinophilic infiltrate, which is poorly responsive to corticosteroids (CS). Elevated levels of inflammatory cytokines, including GM-CSF, IL-6 and IL-17, are found in the airways of SA. Recently, GM-CSF alone or in combination with LPS, was shown to augment expression of IRF5 in macrophages (Mϕ), promoting Th17-driving cytokines. These observations led us to hypothesize that GM-CSF plays an important role in mediating CS-refractory IL-6 production from Mϕ. In RAW 264.7 cells, LPS-induced IL-6 production was inhibited 65% by CS. However, when LPS was combined with GM-CSF at 20 or 200 ng/ml, CS poorly suppressed IL-6 production (17 % and 10.5% respectively). IRF5 expression was detected in LPS+GM-CSF-treated RAW cells and its expression was augmented in the lung-draining lymph nodes of mice exposed to the allergen, house dust mite. Interestingly, IRF5 expression was significantly higher in bronchoalveolar lavage cells isolated from human SA as compared to that in cells from milder, CS-responsive asthmatics or from healthy controls. These observations suggest an important role of GM-CSF and IRF5 in mediating CS-refractory IL-6 production in innate immune cells that in turn promote CS-unresponsive Th17 development and neutrophilic airway inflammation.

Study of Some Factors Associated with High-Risk Asthma in Children

Background: Bronchial asthma is characterized by lower respiratory tract inflammation associated with bronchial hyper responsiveness with variable and reversible airflow obstruction. The majority of asthmatics are sensitized to at least one common allergen. Aim of the study: The aim of this study is to determine the association of high-risk asthma with allergy-related parameters (total serum IgE levels, serum levels of allergen- specific IgE, eosinophil count, eosinophil percentage ) and pulmonary functions in children. Subjects and methods: 50 Children aged 8-15 years diagnosed with atopic asthma were enrolled in the study. Pulmonary function tests, total leukocyte count (TLC), eosinophil count, and eosinophil percentage were estimated. Total serum immunoglobulin E (IgE) levels and serum IgE levels specific to antigens from 1 to 9 allergens with class 1 or higher, namely, Dermatophagoides pteronyssinus (D. pteronyssinus) , Dermatophagoides farina (D. farina ), cat dander , dog dander, cockroach, egg white, milk, Aspergillus fumigatus, and fish, were measured using UniCAP fluoroenzyme immunoassay (FEIA). Results: This study includes 50 participants, 20 (40%) belonged to the high-risk and 30 (60%) to the low-risk groups. This study revealed no significant association in peak expiratory flow rate (PEFR, ％) values between high-risk and low-risk asthma groups (p ˃ 0.05). There was no significant association in forced expiratory volume in first second [ FEV1 (L)] values between high-risk and low-risk asthma groups ( p ˃ 0.05), whereas there was significant association in FEF 25-75% (forced expiratory flow 25-75%) values between high-risk and low-risk asthma groups ( p ˂ 0.05). There was a significant association between total serum IgE level and high-risk asthma, but TLC, eosinophil count, and eosinophil percentage showed non significant association with high-risk asthma. Serum levels of IgE specific to D. pteronyssinus, D. farina, cat dander, and dog dander were significantly associated with high-risk asthma. The high-risk group had higher serum levels of IgE specific to D. pteronyssinus ( p < 0.0001), D. farina ( p < 0.0001), cat dander ( p < 0.0001), and dog dander antigens ( p < 0.0001) compared with those in the low-risk group. There was no significant association between high-risk asthma and the serum levels of IgE specific to antigens from other allergens (including cockroach, egg white, and milk). Serum levels of IgE specific to Aspergillus fumigatus and fish were both negative (class level < 1) in both the high-risk group and the low-risk group. Conclusion Children with higher serum levels of IgE specific to D.pteronyssinus, D. farina, cat dander and dog dander antigens, and total serum IgE levels, and lower FEF25-75% values belong to the high-risk asthma group. The characterization of risk factors has enabled us to identify high-risk asthma in children , leading to better treatment options.

Improving Health status of bronchial asthma patients in Nuclear Materials Authority

Background: Asthma is a common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness and shortness of breath. Asthma can result in variable restriction in the physical, emotional, and social aspects of the patient's life. Setting: out patient clinic in Nuclear materials Authority Objectives: This study was done mainly to Improve health status including symptoms and quality of life in bronchial asthma patients in Nuclear Materials Authority Method: The study was carried out on 51 subjects, they were chosen from those attendants of the out patients clinic in Nuclear Materials Authority in el Katamya in the period from January to May 2012, by measurement of lung function and bronchial hyperresponsiveness as supplemental tools in evaluating the efficacy of treatment with inhaled corticosteroids (ICS) and other controller medications in asthmatic employees. Results: the asthmatic patients were 51 patients (36 males and 15 females), their ages ranged from 27-59 (46.2±7.3) years, they weredetected from those attendants of the out patient clinic in Nuclear Materials Authority in El Katamya representing (2.1% ) of workers. 15 (29.4%) patients were smoker, and 36 (70.6%) patients never smoked, 21 patients (41.2%) were exposed to radioactive materials in their labs in the form of radioactive substances and30 patients (58.8%)patients were not exposed.19 (37.3%) patients had intermittent asthma, 11 (21.6%) patients had mild persistent asthma 9 (17.6%) patients had moderate persistent asthma and 12(23.5%) patients had sever persistent asthma. 11(21.6%) patient used long acting anti-inflammatory medications, 23 (45.1%) patients received other controller medication in the form of short acting steroids as Clenil inhaler and ketotifen as zaditen while the majority of patients received rescue medication 34(66.7%) in the form of short acting bronchodilators and oral steroids. Conclusion: Patient education, measurement of lung function and review of the treatment plan as supplemental tools in evaluating the efficacy of treatment with inhaled corticosteroids and other controller medications in asthmatic employees improve health status including symptoms and quality of life in bronchial asthma patients in Nuclear Materials Authority.

Improving Health status of bronchial asthma patients in Nuclear Materials Authority

Background: Asthma is a common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness and shortness of breath. Asthma can result in variable restriction in the physical, emotional, and social aspects of the patient's life. Setting: out patient clinic in Nuclear materials Authority Objectives: This study was done mainly to Improve health status including symptoms and quality of life in bronchial asthma patients in Nuclear Materials Authority Method: The study was carried out on 51 subjects, they were chosen from those attendants of the out patients clinic in Nuclear Materials Authority in el Katamya in the period from January to May 2012, by measurement of lung function and bronchial hyperresponsiveness as supplemental tools in evaluating the efficacy of treatment with inhaled corticosteroids (ICS) and other controller medications in asthmatic employees. Results: the asthmatic patients were 51 patients (36 males and 15 females), their ages ranged from 27-59 (46.2±7.3) years, they weredetected from those attendants of the out patient clinic in Nuclear Materials Authority in El Katamya representing (2.1% ) of workers. 15 (29.4%) patients were smoker, and 36 (70.6%) patients never smoked, 21 patients (41.2%) were exposed to radioactive materials in their labs in the form of radioactive substances and30 patients (58.8%)patients were not exposed.19 (37.3%) patients had intermittent asthma, 11 (21.6%) patients had mild persistent asthma 9 (17.6%) patients had moderate persistent asthma and 12(23.5%) patients had sever persistent asthma. 11(21.6%) patient used long acting anti-inflammatory medications, 23 (45.1%) patients received other controller medication in the form of short acting steroids as Clenil inhaler and ketotifen as zaditen while the majority of patients received rescue medication 34(66.7%) in the form of short acting bronchodilators and oral steroids. Conclusion: Patient education, measurement of lung function and review of the treatment plan as supplemental tools in evaluating the efficacy of treatment with inhaled corticosteroids and other controller medications in asthmatic employees improve health status including symptoms and quality of life in bronchial asthma patients in Nuclear Materials Authority.

Management of acute exacerbations of chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is characterised by progressive and not fully reversible airflow obstruction. It is a common condition in the UK; it is associated with smoking and becomes more prevalent with age. Symptoms of COPD, such as breathlessness and sputum production, are made worse by acute exacerbations. Such exacerbations may be associated with underlying infection, air pollution or poor medication compliance. Early identification of an exacerbation and appropriate treatment in the community may help avoid unnecessary hospital admission or at least reduce the length of inpatient stay. As well as treating exacerbations appropriately, it is essential that emphasis be placed on prevention, which should include good healthcare advice around smoking cessation, and appropriate disease management for patients diagnosed with COPD.

Inhaled Muscarinic Acetylcholine Receptor Antagonists for Treatment of COPD

Bronchodilators, generally administered via metered dose or dry powder inhalers, are the mainstays of pharmacological treatment of stable COPD. Inhaled long-acting beta-agonists (LABA) and anticholinergics are the bronchodilators primarily used in the chronic treatment of COPD. Anticholinergics act as muscarinic acetylcholine receptor antagonists and are frequently preferred over beta-agonists for their minimal cardiac stimulatory effects and greater efficacy in most studies. Their therapeutic efficacy is based on the fact that vagally mediated bronchoconstriction is the major reversible component of airflow obstruction in patients with COPD. However, bronchodilators are effective only on the reversible component of airflow obstruction, which by definition is limited, as COPD is characterized by a fixed or poorly reversible airflow obstruction. Inhaled anticholinergic antimuscarinic drugs approved for the treatment of COPD include ipratropium bromide, oxitropium bromide and tiotropium bromide. Ipratropium bromide, the prototype of anticholinergic bronchodilators, is a short-acting agent. Oxitropium bromide is administered twice a day. Tiotropium bromide, the only long-acting antimuscarinic agent (LAMA) currently approved, is administered once a day. Newer LAMAs including aclidinium bromide and glycopyrrolate bromide are currently in phase III development for treatment of COPD. Some new LAMAs, including glycocpyrrolate, are suitable for once daily administration and, unlike tiotropium, have a rapid onset of action. New LAMAs and their combination with ultra-LABA and, possibly, inhaled corticosteroids, seem to open new perspectives in the management of COPD. Dual-pharmacology muscarinic antagonist-beta2 agonist (MABA) molecules present a novel approach to the treatment of COPD by combining muscarinic antagonism and beta2 agonism in a single molecule.

La prise en charge de la crise d’asthme au service de pneumologie

Both smokers and patients with asthma can experience fixed airflow obstruction, which is associated with distinctive patterns of airway pathology. The influence of fixed airflow obstruction on the prognosis of these patients is unknown.We sought to investigate lung function decline and exacerbations in a 5-year prospective study of subjects with fixed airflow obstruction due to asthma or chronic obstructive pulmonary disease (COPD). We also sought to explore correlations between functional, pathological, and clinical features.Patients with fixed airflow obstruction due to asthma (n = 16) or COPD (n = 21) and a control group of asthmatic patients with fully reversible airflow obstruction (n = 15) were followed for 5 years.The rates of decline in FEV1 were similar in patients with fixed airflow obstruction caused by asthma (−49.7 ± 10.6 mL/y) or COPD (−51.4 ± 9.8 mL/y) and were higher than in asthmatic patients with reversible airflow obstruction (−18.1 ± 10.1 mL/y, P < .01). Exacerbation rates were also higher in patients with fixed airflow obstruction caused by asthma (1.41 ± 0.26 per patient-year) or COPD (1.98 ± 0.3 per patient-year) compared with those seen in asthmatic patients with reversible airflow obstruction (0.53 ± 0.11 per patient-year, P < .01). Baseline exhaled nitric oxide levels and sputum eosinophil counts correlated with the FEV1 decline in asthmatic patients with fixed airflow obstruction. By contrast, baseline sputum neutrophil counts, emphysema scores, comorbidities, and exacerbation frequency correlated directly and pulmonary diffusion capacity correlated inversely with the FEV1 decline in patients with COPD.In both patients with asthma and those with COPD, fixed airflow obstruction is associated with increased lung function decline and frequency of exacerbations. Nevertheless, the decline in lung function entails the specific pathological and clinical features of the underlying diseases.

Novel Asthma Therapeutics: Insights from Whole-Genome Studies

Asthma is characterized by recurrent and reversible airflow obstruction as well as bronchial hyper-responsiveness. Airway inflammation is central to asthma pathogenesis. Bronchodilators are advocated as rescue treatments for acute asthma symptoms, whereas anti-inflammatory drugs such as Inhaled Corticosteroids (ICS) are common controller therapies for chronic asthma. Leukotriene modifiers are widely prescribed alternatives to ICS. During the past several years, a number of pharmacogenomic studies adopting whole-genome arrays have identified novel gene targets that contribute to the heterogeneity in responses to these anti-asthma drugs. These gene chips contain dense probes that capture either genotypes of single-nucleotide polymorphisms or the expression of genes across the entire human genome. Through these approaches, CLCA1, periostin, serpinB2, FKBP51, NFKB, GLCCI1 and T gene were reported to modulate ICS response in asthma patients whereas ARG1, CRHR2, SPATS2L and COL22A1were novel genes for bronchodilator responses. Some of these therapeutic targets were replicated in independent populations and/or supported by downstream in vitro and in vivo experiments on their functionality. Adequate bioinformatics support was essential in pharmacogenomics research in view of the enormous amount of whole-genome data involved. These whole-genome findings will ultimately facilitate personalized asthma pharmacotherapy that allows us to choose among treatment options that will likely be effective to any particular patient. However, more resources and collaborative efforts are required to advance the pharmacogenomics research.

Dysfunctional lung anatomy and small airways degeneration in COPD

Chronic obstructive pulmonary disease (COPD) is characterized by incompletely reversible airflow obstruction. Direct measurement of airways resistance using invasive techniques has revealed that the site of obstruction is located in the small conducting airways, ie, bronchioles with a diameter < 2 mm. Anatomical changes in these airways include structural abnormalities of the conducting airways (eg, peribronchiolar fibrosis, mucus plugging) and loss of alveolar attachments due to emphysema, which result in destabilization of these airways related to reduced elastic recoil. The relative contribution of structural abnormalities in small conducting airways and emphysema has been a matter of much debate. The present article reviews anatomical changes and inflammatory mechanisms in small conducting airways and in the adjacent lung parenchyma, with a special focus on recent anatomical and imaging data suggesting that the initial event takes place in the small conducting airways and results in a dramatic reduction in the number of airways, together with a reduction in the cross-sectional area of remaining airways. Implications of these findings for the development of novel therapies are briefly discussed.

Severe obstructive disease: Similarities and differences between smoker and non-smoker patients with COPD and/or bronchiectasis

IntroductionPoorly reversible airflow obstruction may or may not be related to smoking. ObjectivesTo describe patients with severe obstructive lung disease including etiology, imaging, functional aspects, systemic manifestations, and the pattern of bronchodilator response. MethodsSixty-eight patients (age 55.9±13.7 years, FEV1 [forced expiratory volume in one second] 31.9±10.2% predicted) underwent spirometry, evaluation of body mass composition, 6-minute walk test, X-ray, thorax high-resolution CT scanning, and clinical evaluation. ResultsOf 68 patients enrolled, 37 had chronic obstructive pulmonary disease (COPD) and 31, extensive bronchiectasis. Among COPD patients the CT scans showed emphysema in 78.4%, and bronchiectasis in 48.6%. There were no significant differences between smokers and non-smokers, except for vital capacity, significantly smaller in non-smokers (p<0.001). We found 29 and 20 volume responders (VR) according to Paré et al. (FEV1/FVC>1=flow responder or <1=VR) and ATS/ERS criteria, respectively. According to Paré et al. criteria, there were 18 patients with FEV1<30% predicted among 29 VR, and 12 with FEV1<30% predicted among 39 without volume response (p=0.0101). ConclusionsIn patients with severe obstruction, smoking does not appear to be relevant in determining functional or systemic differences, and Paré et al. criteria can detect more VR. Bronchiectasis is a common finding in severe COPD.

Aclidinium bromide for the treatment of chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease is characterized by poorly reversible airflow obstruction. Long-acting bronchodilators improve lung function and relieve dyspnea. Aclidinium bromide is a novel long-acting antimuscarinic bronchodilator; Phase III clinical trials have demonstrated that administration of this drug twice per day improves lung function, dyspnea and health-related quality of life. Aclidinium bromide is delivered using the Genuair® device, which is an easy to use multidose dry powder inhaler. Aclidinium bromide is rapidly metabolized in the plasma, so there is low systemic exposure that minimizes the anticholinergic side effects. This new long-acting bronchodilator provides effective bronchodilation with minimal side effects.

Pattern of Use and Cost of Chemotherapy in Breast Cancer Patients Using the NHSO Cancer Protocol in Thailand

Imaging variables, including airway diameter, wall thickness, and air trapping, have been found to be important metrics when differentiating patients with severe asthma from those with nonsevere asthma and healthy subjects.The objective of this study was to identify imaging-based clusters and to explore the association of the clusters with existing clinical metrics.We performed an imaging-based cluster analysis using quantitative computed tomography–based structural and functional variables extracted from the respective inspiration and expiration scans of 248 asthmatic patients. The imaging-based metrics included a broader set of multiscale variables, such as inspiratory airway dimension, expiratory air trapping, and registration-based lung deformation (inspiration vs expiration). Asthma subgroups derived from a clustering method were associated with subject demographics, questionnaire results, medication history, and biomarker variables.Cluster 1 was composed of younger patients with early-onset nonsevere asthma and reversible airflow obstruction and normal airway structure. Cluster 2 was composed of patients with a mix of patients with nonsevere and severe asthma with marginal inflammation who exhibited airway luminal narrowing without wall thickening. Clusters 3 and 4 were dominated by patients with severe asthma. Cluster 3 patients were obese female patients with reversible airflow obstruction who exhibited airway wall thickening without airway narrowing. Cluster 4 patients were late-onset older male subjects with persistent airflow obstruction who exhibited significant air trapping and reduced regional deformation. Cluster 3 and 4 patients also showed decreased lymphocyte and increased neutrophil counts, respectively.Four image-based clusters were identified and shown to be correlated with clinical characteristics. Such clustering serves to differentiate asthma subgroups that can be used as a basis for the development of new therapies.

The lung microbiome in moderate and severe chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is an inflammatory disorder characterized by incompletely reversible airflow obstruction. Bacterial infection of the lower respiratory tract contributes to approximately 50% of COPD exacerbations. Even during periods of stable lung function, the lung harbors a community of bacteria, termed the microbiome. The role of the lung microbiome in the pathogenesis of COPD remains unknown. The COPD lung microbiome, like the healthy lung microbiome, appears to reflect microaspiration of oral microflora. Here we describe the COPD lung microbiome of 22 patients with Moderate or Severe COPD compared to 10 healthy control patients. The composition of the lung microbiomes was determined using 454 pyrosequencing of 16S rDNA found in bronchoalveolar lavage fluid. Sequences were analyzed using mothur, Ribosomal Database Project, Fast UniFrac, and Metastats. Our results showed a significant increase in microbial diversity with the development of COPD. The main phyla in all samples were Actinobacteria, Firmicutes, and Proteobacteria. Principal coordinate analyses demonstrated separation of control and COPD samples, but samples did not cluster based on disease severity. However, samples did cluster based on the use of inhaled corticosteroids and inhaled bronchodilators. Metastats analyses demonstrated an increased abundance of several oral bacteria in COPD samples.

Severe obstructive disease: Similarities and differences between smoker and non-smoker patients with COPD and/or bronchiectasis

IntroductionPoorly reversible airflow obstruction may or may not be related to smoking. ObjectivesTo describe patients with severe obstructive lung disease including etiology, imaging, functional aspects, systemic manifestations, and the pattern of bronchodilator response. MethodsSixty-eight patients (age 55.9±13.7 years, FEV1 [forced expiratory volume in one second] 31.9±10.2% predicted) underwent spirometry, evaluation of body mass composition, 6-minute walk test, X-ray, thorax high-resolution CT scanning, and clinical evaluation. ResultsOf 68 patients enrolled, 37 had chronic obstructive pulmonary disease (COPD) and 31, extensive bronchiectasis. Among COPD patients the CT scans showed emphysema in 78.4%, and bronchiectasis in 48.6%. There were no significant differences between smokers and non-smokers, except for vital capacity, significantly smaller in non-smokers (p<0.001). We found 29 and 20 volume responders (VR) according to Paré et al. (FEV1/FVC>1=flow responder or <1=VR) and ATS/ERS criteria, respectively. According to Paré et al. criteria, there were 18 patients with FEV1<30% predicted among 29 VR, and 12 with FEV1<30% predicted among 39 without volume response (p=0.0101). ConclusionsIn patients with severe obstruction, smoking does not appear to be relevant in determining functional or systemic differences, and Paré et al. criteria can detect more VR. Bronchiectasis is a common finding in severe COPD.

Spleen tyrosine kinase inhibition attenuates airway hyperresponsiveness and pollution-induced enhanced airway response in a chronic mouse model of asthma

Asthma is a chronic inflammatory disease characterized by airways hyperresponsiveness (AHR), reversible airflow obstruction, airway remodeling, and episodic exacerbations caused by air pollutants, such as particulate matter (PM; PM <2.5 μm in diameter [PM(2.5)]) and ozone (O(3)). Spleen tyrosine kinase (Syk), an immunoregulatory kinase, has been implicated in the pathogenesis of asthma. We sought to evaluate the effect of Syk inhibition on AHR in a chronic mouse model of allergic airways inflammation and pollutant exposure. We used a 12-week chronic ovalbumin (OVA) sensitization and challenge mouse model of airways inflammation followed by exposure to PM(2.5) plus O(3). Respiratory mechanics and methacholine (MCh) responsiveness were assessed by using the flexiVent system. The Syk inhibitor NVP-QAB-205 was nebulized intratracheally by using a treatment-based protocol 15 minutes before assessment of MCh responsiveness. Syk expression increased significantly in the airway epithelia of OVA-sensitized and OVA-challenged (OVA/OVA) mice compared with OVA-sensitized but PBS-challenged (OVA/PBS) control mice. OVA/OVA mice exhibited AHR to MCh, which was attenuated by a single administration of NVP-QAB-205 (0.3 and 3 mg/kg). PM(2.5) plus O(3) significantly augmented AHR to MCh in the OVA/OVA mice, which was abrogated by NVP-QAB-205. Total inflammatory cell counts were significantly higher in the bronchoalveolar lavage fluid from OVA/OVA than OVA/PBS mice and were unaffected by PM(2.5) plus O(3) or NVP-QAB-205. NVP-QAB-205 reduced AHR and the enhanced response to PM(2.5) plus O(3) to normal levels in an established model of chronic allergic airways inflammation, suggesting that Syk inhibitors have promise as a therapy for asthma.

DHEA-S inhibits human neutrophil and human airway smooth muscle migration

Airway diseases such as asthma, emphysema, and chronic bronchitis are, in part, characterized by reversible airflow obstruction and inflammation. In severe disease, marked decreases in lung function are associated with airway smooth muscle proliferation and airway neutrophilia. Inhaled glucocorticoids attenuate increased airflow obstruction and airway inflammation that occur, in part, due to increased smooth muscle migration and proliferation, as well as the airway neutrophilia. Glucocorticoids, however, have adverse side effects and, in some patients, are ineffective despite high doses. Recent research has explored the effects of non-traditional steroids on attenuation of inflammation associated with airway diseases. These non-traditional steroids have improved side effect profiles in comparison to glucocorticoid therapy. Our studies assessed effects of dehydroepiandrosterone-3-sulfate (DHEA-S) on migration of both human peripheral blood neutrophils (PMN) and human airway smooth muscle cells (HASM). DHEA-S dose-dependently inhibited chemotaxis of PMN and HASM while having no effect on the phosphorylation levels of Akt, ERK1/2, p38 MAPK or PKC, canonical positive regulators of cell migration. These studies demonstrate direct effects of DHEA-S on cell migration, thereby suggesting that DHEA-S may attenuate airway inflammation and cell migration.

The overlap phenotype: the (missing) link between asthma and COPD.

The definition of chronic obstructive pulmonary dis-ease (COPD) as a preventable and treatable conditioncharacterized by a not completely reversible chronicairflow obstruction [1] is so broad and imprecise thatmany different types of patients with distinct clinicalcharacteristics, prognosis and response to treatmentsmay fit in. These different types are now described as“clinical phenotypes” and the interest in their defin-ition and characterisation is growing [2]. Among thesephenotypes, the so-called overlap of syndromes withairflow obstruction is usually poorly considered [3].In a first step of phenotyping, a COPD patient canpotentially be classified as a predominant parenchymaldestructive or predominant airflow limitation phenotypeby using a few clinical, radiological and functional findings[4]. However, when a patient presents characteristics andsymptoms of two or more respiratory diseases at the sametime, this is described as an overlap syndrome. In particu-lar, the asthma-COPD overlap phenotype has beendescribed as symptoms of increased variability of airflowin association with an incompletely reversible airflowobstruction [5]. From a clinical point of view it usuallycorresponds to individuals diagnosed with asthma beforethe age of 40 who, at an older age, fulfil the criteria forCOPD [6]. Recent estimations of its prevalence report thatabout 13-20% of subjects with COPD have the overlapphenotype [6,7], with an increasing trend in the elderlypopulation (up to 50% in those aged over 70 years) [7].Since they have been systematically excluded from bothCOPD and asthma pharmacological clinical trials as notbeing “pure” subjects, it is clear that we cannot really knowthe response to pharmacological treatment of a significantnumber of patients with COPD.Increased reversibility is one of the key differentialaspects of individuals with the overlap asthma-COPDphenotype. Reversibility in COPD is not only possiblebut it is also not so infrequent: indeed, significant re-versibility in COPD is observed frequently in everydayclinical practice and in a series of patients included in thenewly designed clinical trials [8]. Over one half to almosttwo-thirds of the patients with moderate-to-very-severeCOPD participating in the large clinical trial UPLIFT metthe most commonly used criteria for acute bronchodilatorresponsiveness [9]. In a recent study of COPD patientswithout a prior history of asthma, 44% of the subjectsshowed a positive bronchodilator test with an inverse cor-relation between bronchodilator reversibility and theGOLD severity stages [10].Reversibility, however, has not been considered to be areliable parameter to diagnose or classify patients; thereason being that a patient may be reversible or irrevers-ible in different determinations at different time points[11]. This is a consequence of dichotomising a continu-ous variable as positive or negative. In fact, this approachcould be valid for epidemiologic studies but should neverbe used to guide clinical decisions in an individualpatient. Reversibility in clinical practice must be consid-ered as a continuous variable, and therapeutic decisionsshould be made according to the magnitude of thechange. One example will help to explain this concept: apatient with a reversibility of 11.8% in forced expiratoryvolume in the 1

The diagnosis of asthma, a clinical syndrome

Clinical experience and now genetic data indicate that asthma is a heterogeneous clinical syndrome—clinical cases emerge, proceed and respond to treatments in different ways. Currently the diagnosis of asthma (as...

Serum neurotrophin-3 and neurotrophin-4 levels are associated with asthma severity in children

To the Editors: Asthma is the most common chronic disease in childhood and is characterised by chronic airway inflammation, reversible airflow obstruction and hyperresponsiveness of the airways. Among the substantial pathophysiological aspects of asthma are neuroimmune interaction mechanisms; neurotrophins are mediators of the interactions providing links between immune, structural and neuronal cells. In recent years, several studies have analysed the effects of neurotrophins on allergic inflammation and airway diseases. Elevated brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and neurotrophin-3 (NT-3) levels have been found in bronchoalveolar lavage fluid (BALF) after allergen challenge in allergic asthmatic patients [1,2]. It has also been shown that asthmatic patients demonstrate elevated levels of neurotrophins (NGF and BDNF) in serum and locally in the airways [3,4], and that allergen provocation significantly increases neurotrophin levels in the airways [2]. Increased neurotrophin (BDNF) concentration also correlated with clinical parameters of allergic airway dysfunction, such as airflow limitation and airway hyperresponsiveness, in asthmatic patients [5], whereas its level is normalised after treatment with inhaled corticosteroids [4]. However, to our knowledge, only one study has investigated neurotrophin (BDNF) levels in a paediatric population of asthmatic patients [6]. We hypothesise that given the relationship between neuronal cells and the immune system in asthma, altered peripheral expression of neurotrophins associated with neuronal dysregulation may affect the course of asthma and disease severity in children. The present study was performed on a Polish sample of 98 …

Clinical Phenotypes of COPD: Identification, Definition and Implications for Guidelines

The term phenotype in the field of COPD is defined as “a single or combination of disease attributes that describe differences between individuals with COPD as they relate to clinically meaningful outcomes”. Among all phenotypes described, there are three that are associated with prognosis and especially with a different response to currently available therapies. The phenotypes are: the exacerbator, the overlap COPD-asthma and the emphysema-hyperinflation.The exacerbator is characterized by the presence of, at least, two exacerbations the previous year, and on top of long-acting bronchodilators, may require the use of anti-inflammatory drugs. The overlap phenotype presents symptoms of increased variability of airflow and incompletely reversible airflow obstruction. Due to the underlying inflammatory profile, is used to have a good therapeutic response to inhaled corticosteroids in addition to bronchodilators. Lastly, the emphysema phenotype presents a poor therapeutic response to the existing anti-inflammatory drugs, and long-acting bronchodilators together with rehabilitation are the treatments of choice.Identifying the peculiarities of the different phenotypes of COPD will allow us to implement a more personalized treatment, in which the characteristics of the patients, together with their severity will be key to choose the best treatment option.