Plasma proteins elevated in severe asthma despite oral steroid use and unrelated to Type-2 inflammation.

RATIONALE: Asthma phenotyping requires novel biomarker discovery. OBJECTIVES: To identify plasma biomarkers associated with asthma phenotypes by application of a new proteomic panel to samples from two well-characterised cohorts of severe (SA) and mild-to-moderate (MMA) asthmatics, COPD subjects and healthy controls (HCs). METHODS: An antibody-based array targeting 177 proteins predominantly involved in pathways relevant to inflammation, lipid metabolism, signal transduction and extracellular matrix was applied to plasma from 525 asthmatics and HCs in the U-BIOPRED cohort, and 142 subjects with asthma and COPD from the validation cohort BIOAIR. Effects of oral corticosteroids (OCS) were determined by a 2-week, placebo-controlled OCS trial in BIOAIR, and confirmed by relation to objective OCS measures in U-BIOPRED. RESULTS: In U-BIOPRED, 110 proteins were significantly different, mostly elevated, in SA compared to MMA and HCs. 10 proteins were elevated in SA versus MMA in both U-BIOPRED and BIOAIR (alpha-1-antichymotrypsin, apolipoprotein-E, complement component 9, complement factor I, macrophage inflammatory protein-3, interleukin-6, sphingomyelin phosphodiesterase 3, TNF receptor superfamily member 11a, transforming growth factor-ß and glutathione S-transferase). OCS treatment decreased most proteins, yet differences between SA and MMA remained following correction for OCS use. Consensus clustering of U-BIOPRED protein data yielded six clusters associated with asthma control, quality of life, blood neutrophils, high-sensitivity C-reactive protein and body mass index, but not Type-2 inflammatory biomarkers. The mast cell specific enzyme carboxypeptidase A3 was one major contributor to cluster differentiation. CONCLUSIONS: The plasma proteomic panel revealed previously unexplored yet potentially useful Type-2-independent biomarkers and validated several proteins with established involvement in the pathophysiology of SA.

Prevalence and Population-Attributable Risk for Chronic Airflow Obstruction in a Large Multinational Study.

Rationale: The Global Burden of Disease program identified smoking and ambient and household air pollution as the main drivers of death and disability from chronic obstructive pulmonary disease (COPD). Objectives: To estimate the attributable risk of chronic airflow obstruction (CAO), a quantifiable characteristic of COPD, due to several risk factors. Methods: The Burden of Obstructive Lung Disease study is a cross-sectional study of adults, aged ≥40, in a globally distributed sample of 41 urban and rural sites. Based on data from 28,459 participants, we estimated the prevalence of CAO, defined as a postbronchodilator FEV1-to-FVC ratio less than the lower limit of normal, and the relative risks associated with different risk factors. Local relative risks were estimated using a Bayesian hierarchical model borrowing information from across sites. From these relative risks and the prevalence of risk factors, we estimated local population attributable risks. Measurements and Main Results: The mean prevalence of CAO was 11.2% in men and 8.6% in women. The mean population attributable risk for smoking was 5.1% in men and 2.2% in women. The next most influential risk factors were poor education levels, working in a dusty job for ≥10 years, low body mass index, and a history of tuberculosis. The risk of CAO attributable to the different risk factors varied across sites. Conclusions: Although smoking remains the most important risk factor for CAO, in some areas, poor education, low body mass index, and passive smoking are of greater importance. Dusty occupations and tuberculosis are important risk factors at some sites.

Lung function fluctuation patterns unveil asthma and COPD phenotypes unrelated to type 2 inflammation.

BACKGROUND: In all chronic airway diseases, the dynamics of airway function are influenced by underlying airway inflammation and bronchial hyperresponsiveness along with limitations in reversibility owing to airway and lung remodeling as well as mucous plugging. The relative contribution of each component translates into specific clinical patterns of symptoms, quality of life, exacerbation risk, and treatment success. OBJECTIVE: We aimed to evaluate whether subgrouping of patients with obstructive airway diseases according to patterns of fluctuation in lung function allows identification of specific phenotypes with distinct clinical characteristics. METHODS: We applied the novel method of fluctuation-based clustering (FBC) to twice-daily FEV1 measurements recorded over a 1-year period in a mixed group of 134 adults with mild-to-moderate asthma, severe asthma, or chronic obstructive pulmonary disease from the European BIOAIR cohort. RESULTS: Independently of clinical diagnosis, FBC divided patients into 4 fluctuation-based clusters with progressively increasing alterations in lung function that corresponded to patterns of increasing clinical severity, risk of exacerbation, and lower quality of life. Clusters of patients with airway disease with significantly elevated levels of biomarkers relating to remodeling (osteonectin) and cellular senescence (plasminogen activator inhibitor-1), accompanied by a loss of airway reversibility, pulmonary hyperinflation, and loss of diffusion capacity, were identified. The 4 clusters generated were stable over time and revealed no differences in levels of markers of type 2 inflammation (blood eosinophils and periostin). CONCLUSION: FBC-based phenotyping provides another level of information that is complementary to clinical diagnosis and unrelated to eosinophilic inflammation, which could identify patients who may benefit from specific treatment strategies or closer monitoring.

Diagnosis and management of NSAID-Exacerbated Respiratory Disease (N-ERD)-a EAACI position paper.

NSAID-exacerbated respiratory disease (N-ERD) is a chronic eosinophilic, inflammatory disorder of the respiratory tract occurring in patients with asthma and/or chronic rhinosinusitis with nasal polyps (CRSwNP), symptoms of which are exacerbated by NSAIDs, including aspirin. Despite some progress in understanding of the pathophysiology of the syndrome, which affects 1/10 of patients with asthma and rhinosinusitis, it remains a diagnostic and therapeutic challenge. In order to provide evidence-based recommendations for the diagnosis and management of N-ERD, a panel of international experts was called by the EAACI Asthma Section. The document summarizes current knowledge on the pathophysiology and clinical presentation of N-ERD pointing at significant heterogeneity of this syndrome. Critically evaluating the usefulness of diagnostic tools available, the paper offers practical algorithm for the diagnosis of N-ERD. Recommendations for the most effective management of a patient with N-ERD stressing the potential high morbidity and severity of the underlying asthma and rhinosinusitis are discussed and proposed. Newly described sub-phenotypes and emerging sub-endotypes of N-ERD are potentially relevant for new and more specific (eg, biological) treatment modalities. Finally, the document defines major gaps in our knowledge on N-ERD and unmet needs, which should be addressed in the future.

The utility of biomarkers in diagnosis of aspirin exacerbated respiratory disease.

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is a distinct eosinophilic phenotype of severe asthma with accompanying chronic rhinosinusitis, nasal polyposis, and hypersensitivity to aspirin. Urinary 3-bromotyrosine (uBrTyr) is a noninvasive marker of eosinophil-catalyzed protein oxidation. The lack of in vitro diagnostic test makes the diagnosis of AERD difficult. We aimed to determine uBrTyr levels in patients with AERD (n = 240) and aspirin-tolerant asthma (ATA) (n = 226) and to assess whether its addition to urinary leukotriene E4 (uLTE4) levels and blood eosinophilia can improve the prediction of AERD diagnosis. METHODS: Clinical data, spirometry and blood eosinophilis were evaluated. UBrTyr and uLTE4 levels were measured in urine by HPLC and ELISA, respectively. RESULTS: Both groups of asthmatics (AERD, n = 240; ATA, n = 226) had significantly higher uBrTyr, uLTE4 levels, and blood eosinophils than healthy controls (HC) (n = 71) (p < 0.05). ULTE4 levels and blood eosinophils were significantly higher in AERD as compared to ATA (p = 0.004, p < 0.0001, respectively). whereas uBrTyr levels were not significantly different between both asthma phenotypes (p = 0.34). Asthmatics with high levels of uBrTyr (> 0.101 ng/mg Cr), uLTE4 levels (> 800 pg/mg Cr) and blood eosinophils (> 300 cells/ul) were 7 times more likely to have AERD.. However, uBrTyr did not increase the benefit for predicting AERD when uLTE4 and blood eosinophils were already taken into account (p = 0.57). CONCLUSION: UBrTyr levels are elevated both in AERD and ATA as compared to HC, but they could not differentiate between these asthma phenotypes suggesting a similar eosinophilic activation. The addition of uBrTyr to elevated uLTE4 levels and blood eosinophils did not statistically enhance the prediction of AERD diagnosis.

Prevalence and burden of chronic bronchitis symptoms: results from the BOLD study.

We studied the prevalence, burden and potential risk factors for chronic bronchitis symptoms in the Burden of Obstructive Lung Disease study.Representative population-based samples of adults aged ≥40 years were selected in participating sites. Participants completed questionnaires and spirometry. Chronic bronchitis symptoms were defined as chronic cough and phlegm on most days for ≥3 months each year for ≥2 years.Data from 24 855 subjects from 33 sites in 29 countries were analysed. There were significant differences in the prevalence of self-reported symptoms meeting our definition of chronic bronchitis across sites, from 10.8% in Lexington (KY, USA), to 0% in Ile-Ife (Nigeria) and Blantyre (Malawi). Older age, less education, current smoking, occupational exposure to fumes, self-reported diagnosis of asthma or lung cancer and family history of chronic lung disease were all associated with increased risk of chronic bronchitis. Chronic bronchitis symptoms were associated with worse lung function, more dyspnoea, increased risk of respiratory exacerbations and reduced quality of life, independent of the presence of other lung diseases.The prevalence of chronic bronchitis symptoms varied widely across the studied sites. Chronic bronchitis symptoms were associated with significant burden both in individuals with chronic airflow obstruction and those with normal lung function.

Systemic expression of inflammatory mediators in patients with chronic rhinosinusitis and nasal polyps with and without Aspirin Exacerbated Respiratory Disease.

BACKGROUND: Systemic reactions are related to the pathogenesis of Aspirin Exacerbated Respiratory Disease (AERD). With this work we wanted to study the changes in the systemic levels of inflammatory mediators in both baseline and after oral aspirin challenge in patients with and without AERD. METHODS: Patients with nasal polyposis and asthma with AERD (n=20) and without (n=18) were orally challenged with aspirin in a single-blind placebo controlled study. Serum samples and urine were collected before and 6h after placebo and aspirin oral challenges. Serum levels of inflammatory mediators were assayed by using the Luminex technology and ELISA. The concentrations of 9-alpha, 11-beta prostaglandin F2, and leukotriene E4 (uLTE4) were measured in urine samples by ELISA. The expression of T-cell surface markers was analyzed in peripheral blood mononuclear cells isolated before and after the challenges. RESULTS: AERD patients showed significantly higher baseline levels of s-IL-5R-alpha, uLTE4 and percentage of CD4(+)CD25(+)CD127(pos) and CD4(+)CD45RA(-)CD45RO(+) but decreased levels of TGF-ß1 and number of CD4(+)CD25(+)CD127(neg) cells. Aspirin challenge induced the release of uLTE4, IL-6 and increased the number of CD4(+)CD45RA(-)CD45RO(+) memory T-cells only in AERD patients but failed to reduce the levels of sCD40L as observed in non-AERD subjects. Further, IL-8 and sIL-5R-alpha levels directly correlated with the PD20ASA and the effects of aspirin on IL-6 and number of memory T-cells was more pronounced in subjects showing more strong reaction (bronchial and nasal). CONCLUSIONS: AERD patients have a differential baseline inflammatory pattern that supports the role inflammation as underlying mechanism of the disease. Systemic response to oral aspirin challenge was related to an increase in serum IL-6 and the number of circulating memory T-cells in AERD patients.

Certain subphenotypes of aspirin-exacerbated respiratory disease distinguished by latent class analysis.

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is recognized as a distinct asthma phenotype. It usually has a severe course accompanied by chronic hyperplastic eosinophilic sinusitis with nasal polyps, blood eosinophilia, and increased concentrations of urinary leukotriene E4 (LTE4). More insightful analysis of individual patients shows this group to be nonhomogeneous. OBJECTIVE: We sought to identify any likely subphenotypes in a cohort of patients with AERD through the application of latent class analysis (LCA). METHODS: Clinical data from 201 patients with AERD (134 women) were collected from questionnaires. Standard spirometry, atopy traits, blood eosinophilia, and urinary LTE4 concentrations were evaluated. LCA was applied to identify possible AERD subphenotypes. RESULTS: Four classes (subphenotypes) within the AERD phenotype were identified as follows: class 1, asthma with a moderate course, intensive upper airway symptoms, and blood eosinophilia (18.9% of patients); class 2, asthma with a mild course, relatively well controlled, and with low health care use (34.8% of patients); class 3, asthma with a severe course, poorly controlled, and with severe exacerbations and airway obstruction (41.3% of patients); and class 4, poorly controlled asthma with frequent and severe exacerbations in female subjects (5.0% of patients). Atopic status did not affect class membership. Patients with particularly intensive upper airway symptoms had the highest levels of blood eosinophilia and the highest concentrations of urinary LTE4. CONCLUSIONS: LCA revealed unique AERD subphenotypes, thus corroborating the heterogeneity of this population. Such discrimination might facilitate more individualized treatment in difficult-to-treat patients.

Aspirin desensitization in patients with aspirin-induced and aspirin-tolerant asthma: a double-blind study.

BACKGROUND: Numerous open trials have demonstrated the beneficial clinical effects of aspirin desensitization (AD) in patients with aspirin-induced asthma (AIA). These beneficial effects might be attributable to aspirin's potent anti-inflammatory properties, but that supposition requires further corroboration. OBJECTIVE: We sought to compare the clinical and biochemical responses to chronic oral AD in 20 patients with AIA and 14 patients with aspirin-tolerant asthma (ATA). All of the patients had chronic rhinosinusitis and nasal polyposis, and these responses were investigated in a pilot, double-blind, placebo-controlled study. METHODS: Twelve patients with AIA and 6 patients with ATA were randomly assigned to receive 624 mg of aspirin, and 8 patients with AIA and 8 patients with ATA received placebo. Both aspirin and placebo were administered once daily for 6 months. Nasal symptoms, Sino-Nasal Outcome Test (SNOT20) scores, peak nasal inspiratory flows, Asthma Control Questionnaire scores, spirometric parameters, peak expiratory flows, blood eosinophilia, and corticosteroid doses were assessed on a monthly basis. Levels of urinary leukotriene E4 and the stable plasma prostaglandin (PG) D2 metabolite 9α,11ß-PGF2 were evaluated at baseline and after 1, 3, 5, and 6 months. RESULTS: Only the patients with AIA subjected to AD reported improvements in smell and reductions in sneezing and nasal blockade. The SNOT20 and Asthma Control Questionnaire scores of these patients decreased, and their peak nasal inspiratory flows increased. The dosages of inhaled corticosteroids were reduced. There were no changes in leukotriene E(4) or 9α,11ß-PGF(2) levels after AD. CONCLUSION: The clinically beneficial effects of AD on nasal and bronchial symptoms occurred only in the patients with AIA.

Arterial and venous thromboembolism in chronic obstructive pulmonary disease: from pathogenic mechanisms to prevention and treatment.

Chronic obstructive pulmonary disease (COPD) affects approximately 10% of adults older than 40 years and is an important causes of disability and death in elderly subjects. A large proportion of COPD patients suffer from cardiovascular comorbidities. Thromboembolic events contribute considerably to morbidity and mortality in these subjects. This review summarizes the current evidence regarding the association of COPD with increased thromboembolic risk. We discuss multiple mechanisms potentially linking these conditions and available pharmacological interventions reducing the risk of thrombotic arterial and venous events with special attention paid to new oral anticoagulants.

Chronic obstructive pulmonary disease mortality and prevalence: the associations with smoking and poverty--a BOLD analysis.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a commonly reported cause of death and associated with smoking. However, COPD mortality is high in poor countries with low smoking rates. Spirometric restriction predicts mortality better than airflow obstruction, suggesting that the prevalence of restriction could explain mortality rates attributed to COPD. We have studied associations between mortality from COPD and low lung function, and between both lung function and death rates and cigarette consumption and gross national income per capita (GNI). METHODS: National COPD mortality rates were regressed against the prevalence of airflow obstruction and spirometric restriction in 22 Burden of Obstructive Lung Disease (BOLD) study sites and against GNI, and national smoking prevalence. The prevalence of airflow obstruction and spirometric restriction in the BOLD sites were regressed against GNI and mean pack years smoked. RESULTS: National COPD mortality rates were more strongly associated with spirometric restriction in the BOLD sites (<60 years: men rs=0.73, p=0.0001; women rs=0.90, p<0.0001; 60+ years: men rs=0.63, p=0.0022; women rs=0.37, p=0.1) than obstruction (<60 years: men rs=0.28, p=0.20; women rs=0.17, p<0.46; 60+ years: men rs=0.28, p=0.23; women rs=0.22, p=0.33). Obstruction increased with mean pack years smoked, but COPD mortality fell with increased cigarette consumption and rose rapidly as GNI fell below US$15 000. Prevalence of restriction was not associated with smoking but also increased rapidly as GNI fell below US$15 000. CONCLUSIONS: Smoking remains the single most important cause of obstruction but a high prevalence of restriction associated with poverty could explain the high 'COPD' mortality in poor countries.

Comparison of IGRA tests and TST in the diagnosis of latent tuberculosis infection and predicting tuberculosis in risk groups in Krakow, Poland.

BACKGROUND: The objective of this study was to assess the prevalence of latent tuberculosis infection (LTBI) in risk groups in Krakow, using the QuantiFERON-TB Gold In-Tube (QFT-GIT) test and the tuberculin skin test (TST); we also sought to assess the rate of progression to active disease over 4-5 y of follow-up. METHODS: QFT-GIT tests were performed on 785 subjects and the TST on 701 subjects from the risk groups of homeless persons, close contacts, periodic contacts, and residents of long-term care facilities (LTCFs), and subjects from a low risk group. RESULTS: In homeless persons, close contacts, periodic contacts, LTCF residents, and low risk persons, a positive QFT-GIT was found in 36.7%, 27.2%, 27.0%, 21.1%, and 23.7% of subjects, respectively, while a positive TST was found in 55.8%, 47.4%, 47.6%, 43.2%, and 47.9%, respectively. Of 63 homeless subjects, 5 developed active TB over 248 person-y of follow-up (incidence rate (IR) 20 per 1000 person-y, 95% confidence interval (CI) 8.4-48.5); of 148 close contacts, 5 developed active TB over 740 person-y of follow-up (IR 7, 95% CI 2.8-16.2); of 145 periodic contacts, 2 developed active TB over 580 person-y of follow-up (IR 4, 95% CI 0.9-13.8). The IR per 1000 person-y (95% CI) among subjects with a positive QFT-GIT was 30 (9.0-86.1) for homeless subjects, 18 (5.7-54.7) for close contacts, and 13 (3.2-51.3) for periodic contacts. In Poland there is no policy for the provision of LTBI treatment to people with a positive QFT or TST; therefore, the estimated rates of disease progression were analysed amongst untreated subjects. CONCLUSIONS: The prevalence of positive QFT-GIT and TST was high in the study risk groups. The best predictor of active TB in the homeless and close contacts groups was a positive QFT-GIT together with a positive TST.

Detection of exacerbations in asthma based on electronic diary data: results from the 1-year prospective BIOAIR study.

BACKGROUND: Objective measures are required that may be used as a proxy for exacerbations in asthma. The aim was to determine the sensitivity and specificity of electronic diary data to detect severe exacerbations (SEs) of asthma. A secondary aim was to identify phenotypic variables associated with a higher risk of exacerbation. METHODS: In the BIOAIR study, 169 patients with asthma (93 severe (SA); 76 mild to moderate (MA)) recorded lung function, symptoms and medication use in electronic diaries for 1 year. Data were analysed using receiver-operator characteristics curves and related to physician-diagnosed exacerbations. Medical history and baseline clinical data were used to assess risk of exacerbation. RESULTS: Of 122 physician-diagnosed exacerbations, 104 occurred in the SA group (1.1 per patient/year), 18 in the MA group (0.2 per patient/year) and 63 were severe using American Thoracic Society/European Respiratory Society criteria. During exacerbations, peak expiratory flow (PEF) and forced expiratory volume in 1 s significantly decreased, whereas day and night symptoms significantly increased. An algorithm combining a 20% decrease in PEF or a 20% increase in day symptoms on 2 consecutive days was able to detect SEs with 65% sensitivity and 95% specificity. The strongest risk factors for SEs were low Asthma Control Questionnaire score, sputum eosinophils ≥ 3%, body mass index >25 and low quality of life (St George's Respiratory Questionnaire), with ORs between 3.61 and 2.22 (p<0.05). CONCLUSIONS: Regular electronic monitoring of PEF and asthma symptoms provides an acceptable sensitivity and specificity for the detection of SEs and may be suitable for personal internet-based monitoring of asthma control.

Clinical management of patients with a history of urticaria/angioedema induced by multiple NSAIDs: an expert panel review.

Nonsteroidal anti-inflammatory drugs (NSAIDs) represent one of the most frequent causes of drug-induced urticaria/angioedema worldwide. Recent review articles have classified patients experiencing NSAID-induced urticaria/angioedema into different categories, including single reactors, multiple reactors, and multiple reactors with underlying chronic urticaria. Each of these categories requires a different clinical approach. The present article, written by a panel of experts, reports the main recommendations for the practical clinical management of patients with a history of urticaria/angioedema induced by multiple NSAID based on current knowledge.

Transthyretin amyloidosis with pulmonary involvement in a patient with monoclonal gammapathy.

Pulmonary involvement in the course of systemic senile amyloidosis caused by non-mutated transthyretin is rarely described. We report on concomitant monoclonal gammapathy of undermined significance (MGUS) and amyloidosis with non-mutated transthyretin with diffuse lesions in lung parenchyma. A female patient, 67 years old, was admitted with dyspnoea, malaise, weight loss, and disseminated radiological lesions in the lungs. On lung HRCT, signs of pulmonary hypertension, alveolar and interstitial involvement, with thickening of septal lines were found. Echocardiography revealed severe pulmonary hypertension, and electromyography revealed sensoromotoric polyneuropathy with axon and myelin damage. Pathological assessment of lung specimens revealed nodular deposits of amyloid in the bronchial walls and lung parenchyma Congo red staining was positive. Specimens of colon mucosa confirmed amyloidosis. Stainings for AA, AL and beta2-microglobulin were negative but were positive for transthyretin. Bone marrow trepanobiopsy indicated monoclonal gammapathy of MGUS type; Congo red staining was positive. Transthyretin amyloidosis with vascular involvement, particularly of arteriovenous anastomoses, including pulmonary vessels and an insignificant amount of AL protein (perhaps secondary imbibition with AL protein from serum) was diagnosed in amyloid deposits. No mutations of the transthyretin gene (exon 1,2,3,4) were found. The patient was treated with methylprednisolone, melphalan and then with cyclophosphamide. Radiological examinations performed 1 and 2 month/s after initiation of therapy showed progression of pulmonary lesions. The patient died one month later; an autopsy was not performed.

Worldwide patterns of bronchodilator responsiveness: results from the Burden of Obstructive Lung Disease study.

RATIONALE: Criteria for a clinically significant bronchodilator response (BDR) are mainly based on studies in patients with obstructive lung diseases. Little is known about the BDR in healthy general populations, and even less about the worldwide patterns. METHODS: 10 360 adults aged 40 years and older from 14 countries in North America, Europe, Africa and Asia participated in the Burden of Obstructive Lung Disease study. Spirometry was used before and after an inhaled bronchodilator to determine the distribution of the BDR in population-based samples of healthy non-smokers and individuals with airflow obstruction. RESULTS: In 3922 healthy never smokers, the weighted pooled estimate of the 95th percentiles (95% CI) for bronchodilator response were 284 ml (263 to 305) absolute change in forced expiratory volume in 1 s from baseline (ΔFEV(1)); 12.0% (11.2% to 12.8%) change relative to initial value (%ΔFEV(1i)); and 10.0% (9.5% to 10.5%) change relative to predicted value (%ΔFEV(1p)). The corresponding mean changes in forced vital capacity (FVC) were 322 ml (271 to 373) absolute change from baseline (ΔFVC); 10.5% (8.9% to 12.0%) change relative to initial value (ΔFVC(i)); and 9.2% (7.9% to 10.5%) change relative to predicted value (ΔFVC(p)). The proportion who exceeded the above threshold values in the subgroup with spirometrically defined Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 2 and higher (FEV(1)/FVC <0.7 and FEV(1)% predicted <80%) were 11.1%, 30.8% and 12.9% respectively for the FEV(1)-based thresholds and 22.6%, 28.6% and 22.1% respectively for the FVC-based thresholds. CONCLUSIONS: The results provide reference values for bronchodilator responses worldwide that confirm guideline estimates for a clinically significant level of BDR in bronchodilator testing.

Mild asthmatics benefit from music therapy.

OBJECTIVE: The aim of the study was to evaluate the effectiveness of pulmonary rehabilitation with music therapy in patients with asthma. METHODS: Seventy-six selected inpatients (54 women and 22 men; mean age = 56.4 years; SD = 11.8) with stable asthma underwent pulmonary rehabilitation in two groups: standard versus music therapy. RESULTS: After the intervention, an increase in analyzed spirometric values (forced expiratory volume at the first second (FEV(1)), FEV(1) as a percentage of vital capacity (FEV(1) % FVC), forced expiratory flow at 25%, 50%, and 75% of vital capacity (FEF(25), FEF(50), and FEF(75), respectively), and peak expiratory flow) was observed in both the groups (p < .05) but without any intergroup differences (p > .05). A greater increase of mean FEV(1) % FVC, FEF(50), and FEF(75) values was observed only in the patients with mild asthma from the music therapy group (p < .05). In both the groups, a dyspnea reduction was noted (p < .001). However, it was influenced neither by the type of rehabilitation nor by the gender (p > .05), but the interaction of these variables was significant (p = .044). A dyspnea reduction was observed in women in both the groups (p < .001) and in men in the music therapy group only (p = .001). A change in the value of anxiety (6.43, SD = 7.73) on the 10th day compared with the first day of the study was noticed (p < .001). However, this change was not influenced by the type of rehabilitation, gender, or a combination of these two variables (p > .05). CONCLUSION: Music therapy improves the respiratory function in patients with mild asthma and reduces dyspnea mainly in men with asthma.

Targeted eicosanoid lipidomics of exhaled breath condensate provide a distinct pattern in the aspirin-intolerant asthma phenotype.

BACKGROUND: Eicosanoids, important signaling and inflammatory molecules, are present in exhaled breath condensate (EBC) in very low concentrations, requiring highly sensitive analytic methods for their quantification. OBJECTIVE: We sought to assess a vast platform of eicosanoids in different asthma phenotypes, including aspirin-intolerant asthma, by means of a recently developed analytic approach based on mass spectrometry. METHODS: EBC from 115 adult asthmatic subjects (62 with aspirin intolerance) and 38 healthy control subjects were assessed quantitatively for 19 eicosanoids by using complementary HPLC, gas chromatography-mass spectrometry, or both. Palmitic acid concentrations were used as a marker for dilution of condensate samples. RESULTS: Asthma was characterized by an increase in arachidonate lipoxygenase products and cysteinyl leukotrienes. The COX pathway was also significantly upregulated in asthmatic subjects. Subjects with aspirin-intolerant asthma were distinguished by a sharp increase in the level of prostaglandin D(2) and E(2) metabolites; their 5- and 15-hydroxyeicosateraenoic acid levels were also higher than in aspirin-tolerant subjects. A classical discriminant analysis permitted us to classify correctly 99% of asthmatic subjects within the study population; the specificity of the analysis was 97%. The eicosanoid profiling allowed for 92% correct classification of aspirin-intolerant subjects. CONCLUSIONS: The highly sensitive eicosanoid profiling in EBC makes it possible to detect alterations in asthma, especially in its distinct phenotype characterized by hypersensitivity to aspirin and other nonsteroidal anti-inflammatory drugs. This permits us to discriminate asthmatic subjects from healthy subjects, as well as to distinguish the 2 asthma phenotypes based on the presence or absence of aspirin hypersensitivity.

[Effects of biomass combustion and occupational exposures on lung function in random population sample of Malopolska inhabitants]. / Wplyw spalania biomasy i narazen zawodowych na czynnosc pluc w losowej próbie populacyjnej mieszkanców Malopolski.

INTRODUCTION: Risk factors other than tobacco smoking contribute to about 20% of chronic obstructive pulmonary disease cases. Exposure to these risk factors and their influence on lung function has not been adequately studied in the population of Malopolska. MATERIAL AND METHODS: In random population sample of adults at least forty years old, residents of 2 districts of Malopolska, data on exposure to known and probable respiratory risk factors were collected using questionnaire. All subjects without contraindications performed pre- and post-bronchodilatator spirometry. RESULTS: We analyzed data from 618 subjects; 94,8% subjects lived for longer than 6 months in a dwelling where stove using coal or wood has been used for cooking and/or heating. At the time of study as many as 32.5% subjects were still using coal or wood for cooking or heating. Coal or wood were used as fuel on average for more than 30 years; 67% of subjects have ever worked in professions carrying a risk of exposure to potential respiratory risk factors. We have identified an independent relationship of farming with lower FEV1/FVC values as well as increased chronic obstructive pulmonary disease risk. CONCLUSIONS: Significant proportion of Malopolska inhabitants has been exposed to risks associated with cooking or heating with coal or wood. In the studied population farming was related to increased risk of chronic obstructive respiratory disease.

[Measurement of bronchoconstrictive eicosanoids in chronic obstructive pulmonary disease]. / Pomiar bronchospastycznych eikozanoidów w przewleklejobturacyjnej chorobie pluc.

INTRODUCTION: The aim of the study was the evaluation of the concentration of 9α11ß prostaglandin F(2) - a stable metabolite of prostaglandin D(2) (PGD(2)) and leukotriene E(4) (LTE(4)) in stable and exacerbated COPD patients. MATERIAL AND METHODS: 29 COPD patients aged 73 ± 8.34, mean FEV1 = 48.64 ± 15.75% of predictive value and 29 healthy controls aged 57.48 ± 10.86, mean FEV1 = 97.17 ± 13.81% of predictive value participated in this study. Samples of urine and blood were taken from COPD patients during exacerbation and in stable state of the disease; LTE(4) was determined in urine using commercial enzyme immunoassay (EIA) and 9α11ß prostaglandin F(2) (9α11ßPGF(2)) - stable metabolite of PGD(2) was evaluated in blood and urine using GC/MS. RESULTS: LTE(4) concentration in urine (677.15 vs. 436.4 pg/mg of creatinine; p = 0.035) and 9α11ßPGF(2) in blood serum (5.35 vs. 3.07 pg/ml; p = 0.007) were significantly higher in exacerbated COPD patients than in control group. There was no difference in LTE(4) level in urine and 9α11ßPGF2 in blood serum between exacerbated and stable COPD. The urinary 9α11ßPGF(2) concentration did not differ between all studied groups. We found a positive correlation between smoking history and the urine LTE(4) level (r = 0.395; p = 0.002) as well as blood 9α11ßPGF(2) concentration (r = 0.603; p = 0.001) in COPD patients. CONCLUSIONS: 9α11ßPGF(2) and LTE(4) level in urine did not differ between the stable COPD group and the control group. We also did not find any difference between LTE4 level in urine and 9α11ßPGF(2) in blood and urine between exacerbated and stable COPD. Finally, LTE(4) concentration in urine and 9α11ßPGF(2) in blood occurred to be significantly higher in exacerbated COPD patients than in control group.