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Background Side-effect concerns impede adherence with inhaled corticosteroids ( ICS) and often underlie poor asthma control. We developed a brief version ( ICQ-S) of the 57-item Inhaled Corticosteroids side-effect Questionnaire ( ICQ) to facilitate side-effect monitoring in busy clinics. Methods Part 1: After completion by 482 patients with doctor-diagnosed asthma, each ICQ item underwent item reduction analysis. Part 2: Patients prescribed ICS for asthma completed the ICQ at baseline ( BL), ICQ-S at day 14 (D14) and day 28 (D28), and 6-item Asthma Control Questionnaire ( ACQ) and Mini Asthma Quality of Life Questionnaire (Mini AQLQ) at BL, D14 and D28. 14-day test-retest reliability was assessed by intraclass correlation coefficient ( ICC) between ICQ-S scores and internal consistency by Cronbach's alpha (α) coefficient and item-total correlations of ICQ-S. Criterion validity was assessed by correlations (Spearman's rho) between ICQ and ICQ-S total score. Patients reported duration and difficulty of ICQ-S completion at D28. Results Part 1: The ICQ-S consists of fifteen local/systemic ICS side-effects of similar range to the full ICQ. Part 2: 62 asthma patients (mean ACQ score 0.79 ± SD 0.83) prescribed daily ICS [ BDP-equivalent median dose 1000 μg ( IQR: 500, 1000)] participated. ICC between ICQ-S scores was 0.90. All item-total correlations were rho ≥ 0.20. The ICQ-S demonstrated criterion validity, for example, ICQ and ICQ-S were strongly associated (rho = 0.86). 81% of patients completed the ICQ-S within 5 minutes and 97% found completion 'not difficult'. Conclusion The ICQ-S is a brief, patient-friendly tool with good reliability and validity, which may be useful for monitoring ICS side-effects in clinical practice. [ABSTRACT FROM AUTHOR]

Background Bronchial hyperresponsiveness ( BHR) can be present in subjects without any respiratory symptoms. Little is known about the role of the small airways in asymptomatic subjects with BHR. Methods We investigated small airway function assessed by spirometry and impulse oscillometry, as well as Borg dyspnea scores at baseline and during a methacholine provocation test in 15 subjects with asymptomatic BHR, 15 asthma patients, and 15 healthy controls. Results At baseline, small airway function ( R5- R20 and X5) was comparable between subjects with asymptomatic BHR and healthy controls, whereas asthma patients showed small airway dysfunction as reflected by higher R5- R20 and lower X5 values. During methacholine provocation, small airway dysfunction was more severe in asthma patients than in subjects with asymptomatic BHR. Interestingly, a higher increase in small airway dysfunction during methacholine provocation was associated with a higher increase in Borg dyspnea scores in subjects with asymptomatic BHR, but not in asthma patients. Conclusion Subjects with asymptomatic BHR may experience fewer symptoms in daily life because they have less small airway dysfunction. [ABSTRACT FROM AUTHOR]

Background The incidence of asthma and obesity is increasing worldwide, and reports suggest that obese patients have more severe asthma. We investigated whether obese asthma patients have more severe airway obstruction and airway hyper-responsiveness and a different type of airway inflammation than lean asthmatics. Furthermore, we assessed the effect of obesity on corticosteroid treatment response. Methods Patient data from four well-documented asthma cohorts were pooled ( n = 423). We evaluated FEV1, bronchial hyper-responsiveness ( PC20) to either methacholine/histamine or adenosine 5′-monophosphate ( AMP) (differential) cell counts in induced sputum and blood and corticosteroid treatment response in 118 patients. Results At baseline, FEV1, PC20 methacholine or histamine, and PC20 AMP values were comparable in 63 obese ( BMI ≥30 kg/m2) and 213 lean patients ( BMI <25 kg/m2). Obese patients had significantly higher blood neutrophils. These higher blood neutrophils were only seen in obese women and not in obese men. After a two-week treatment with corticosteroids, we observed less corticosteroid-induced improvement in FEV1%predicted in obese patients than in lean patients (median 1.7% vs 6.3% respectively, P = 0.04). The percentage of sputum eosinophils improved significantly less with higher BMI ( P = 0.03), and the number of blood neutrophils increased less in obese than in lean patients (0.32 x103/μl vs 0.57 x103/μl, P = 0.046). Conclusions We found no differences in asthma severity between obese and nonobese asthmatics. Interestingly, obese patients demonstrated more neutrophils in sputum and blood than nonobese patients. The smaller improvement in FEV1 and sputum eosinophils suggests a worse corticosteroid treatment response in obese asthmatics. [ABSTRACT FROM AUTHOR]

Background: Inhaled corticosteroids (ICS) provide short term benefits in asthma but the long term effects are still unknown. Methods: 281 patients diagnosed with moderate to severe asthma in 1963-75 were re-examined in 1991-9. Information was collected on forced expiratory volume in 1 second (FEV1), bronchial hyperresponsiveness, atopy, smoking, use and dosage of oral and ICS. Patients were included in the analyses if they had at least three FEV1 measurements during two consecutive years after the age of 30 and used ICS during follow up. Results: Analyses were performed on 122 patients. During a median follow up period of 23 years, 71 men and 51 women had on average 37 and 40 individual FEV1 measurements, respectively. Linear mixed effect models showed that men had a mean annual decline in FEV1 of 20.6 mI/year less after ICS initiation than before (p=0.011), and in women the decline in FEV1 was 3.2 mI/year less (p=0.73). In individuals with <5 pack years of smoking the decline in FEV1 was 36.8 mI/year less after ICS institution in men (p=0.0097) and 0.8 mI/year less in women (p=0.94), the difference between the sexes being significant (p=O.O45). These effects were not observed in those with ⩾5 pack years smoking. A higher daily dose of ICS was associated with a smaller decline in FEV1 in men (p=0.006), an effect not observed in women. Conclusion: Treatment with ICS in adult patients with moderate to severe asthma was associated with a reduction in the decline in FEV1 over a 23 year follow up period in men who had smoked <5 pack years. This effect was dose dependent and was not present in women or in men with ⩾5 pack years of smoking at follow up. The lack of effect of ICS on the decline in FEV1 in women needs further study. [ABSTRACT FROM AUTHOR]

Summary Background In asthma patients, bronchial hyper-responsiveness (BHR) to adenosine-5′-monophosphate (AMP) reflects bronchial inflammation more closely than BHR to methacholine. In this follow-up study we studied bronchial responsiveness to both stimuli as predictors of new-onset airway symptoms. Methods We included 118 laboratory animal workers and bakery apprentices with a work experience of maximally 1 year. The baseline survey comprised a questionnaire, skin prick tests (SPTs) to common and work allergens, blood eosinophil counting, and bronchial challenge with methacholine and AMP. At follow-up, questionnaire and SPTs to work allergens were repeated. Airway symptoms to common allergens and work allergens were defined as nasal symptoms, chest tightness or asthma attack during or after contact with either common or work allergen. Bronchial challenge tests were analysed by BHR at a 15% fall in forced expiratory volume of 1 s (FEV1 ), and by dose–response-slope (DRS). Results Fourteen subjects (12%) developed airway symptoms to work allergens, of whom 12 had nasal symptoms. A positive SPT to work allergens occurred in 64%, and was the strongest predictor of airway symptoms [relative risk (RR) 7.5, 95% confidence interval (CI) 2.0–28.6]. Other predictors were airway symptoms to common allergens (RR 4.3, 95% CI 1.4–12.8), blood hypereosinophilia (RR 4.4, 95% CI 1.2–15.4) and BHR, with a slightly higher risk estimate for AMP than for methacholine (RRAMP 3.7, 95% CI 1.1–12.5 and RRmeth 2.8, 95% CI 1.0–8.5). The difference was more distinct analysing airway responsiveness by DRS, for which AMP predicted symptoms better than methacholine (P < 0.05). Conclusions Pre-existent bronchial inflammation or a preinflammatory state marked by AMP (hyper)responsiveness increases the vulnerability to develop nasal symptoms. [ABSTRACT FROM AUTHOR]

Background Dendritic cells (DC) are the most potent antigen-presenting cells (APC) and stimulators of T cells. Dendritic cells are also likely to be essential for the initiation of allergic immune responses in the lung. However, there are not many data on the presence of dendritic cells in the airways of patients with atopic asthma and on the effects of corticosteroid-treatment on such dendritic cells. Objective We investigated the distribution of dendritic cells in the bronchial epithelium and mucosa of 16 non-smoking atopic asthmatic patients and eight healthy control subjects using detailed immunohistochemistry (CD1a, HLA-DR, L25 as markers for dendritic cells). Methods Eleven asthmatics were treated for 2.5 years with bronchodilators only and five with bronchodilators and inhaled beclomethasone dipropionate (BDP), 800 μg daily. The patients were randomly sampled from a double-blind multicentre study. Results There were higher numbers of CD1a+ DC ( P = 0.003), L25+ DC (P = 0.002) and HLA-DR expression (P = 0.042) in the bronchial mucosa of asthmatic patients compared with healthy controls. After 2.5 years of treatment, we found a significant increase in flow expiratory volume in 1 second (FEV1) (P = 0.009) and a significant decrease in hyperresponsiveness (PC20 histamine) (P = 0.013) in the corticosteroid group (n = 5) compared with the bronchodilator group (n = 11). This clinical improvement in the corticosteroid-treated group was accompanied by significantly lower numbers of CD1a+ DC (P = 0.008), and HLA-DR expression (P = 0.028) in the bronchial mucosa than in the bronchodilator-treated group. Conclusion Our data suggest that dendritic cells are involved in asthmatic inflammation and that corticosteroids may downregulute the number of dendritic. [ABSTRACT FROM AUTHOR]

Type-2 low asthma affects 30-50% of people with severe asthma and includes a phenotype characterized by sputum neutrophilia and resistance to corticosteroids. Airways inflammation in type-2 low asthma or COPD is potentially driven by persistent bacterial colonization of the lower airways by bacteria such as non-encapsulated Haemophilus influenzae (NTHi). Although pathogenic in the lower airways, NTHi is a commensal of the upper airways. It is not known to what extent these strains can invade airway epithelial cells, persist intracellularly and activate epithelial cell production of proinflammatory cytokines, and how this differs between the upper and lower airways. We studied NTHi infection of primary human bronchial epithelial cells (PBECs), primary nasal epithelial cells (NECs) and epithelial cell lines from upper and lower airways. NTHi strains differed in propensity for intracellular and paracellular invasion. We found NTHi was internalized within PBECs at 6 h, but live intracellular infection did not persist at 24 h. Confocal microscopy and flow cytometry showed NTHi infected secretory, ciliated and basal PBECs. Infection of PBECs led to induction of CXCL8, interleukin (IL)-1β, IL-6 and TNF. The magnitude of cytokine induction was independent of the degree of intracellular invasion, either by differing strains or by cytochalasin D inhibition of endocytosis, with the exception of the inflammasome-induced mediator IL1β. NTHi-induced activation of TLR2/4, NOD1/2 and NLR inflammasome pathways was significantly stronger in NECs than in PBECs. These data suggest that NTHi is internalized transiently by airway epithelial cells and has capacity to drive inflammation in airway epithelial cells. [ABSTRACT FROM AUTHOR]

Background Anti-allergic mattress encasing may provide clinical benefit in asthmatic patients. However, the effect of mattress encasings on allergen-specific parameters, such as bronchial reactions to house dust mite (HDM) challenge, is not clear. Objective To investigate the effect of anti-allergic mattress encasings on allergen sensitivity in patients with moderate to severe asthma. Methods Twenty-seven patients with asthma and HDM allergy were studied in a double-blind, placebo-controlled study. Concentrations of Dermatophagoides pteronyssinus (Der p 1) were measured in mattress dust before and after 1 year of treatment; bronchial histamine challenge, bronchial challenge with HDM and intradermal skin challenges with HDM were performed. The number of eosinophils in peripheral blood was assessed. Results In the active group, but not in the placebo group, there was a significant reduction in Der p 1 concentration in the dust collected from the mattresses after 1 year of treatment compared to before. There was a significant difference between the groups with respect to HDM-induced early-reaction (ER) in the airways and the number of blood eosinophils, which reflected an increase in ER and eosinophils in the placebo group without significant change in the active group. No significant improvement in PC20 histamine, late-reaction (LR) and skin tests was found in either groups. Conclusion Our data suggest that encasings protect against a further increase in allergen sensitivity in asthmatic patients, so their use should be recommended. [ABSTRACT FROM AUTHOR]

Asthma affects an estimated 262 million people worldwide and caused over 461,000 deaths in 2019. The disease is characterized by chronic airway inflammation, reversible bronchoconstriction, and airway remodeling. Longitudinal studies have shown that current treatments for asthma (inhaled bronchodilators and corticosteroids) can reduce the frequency of exacerbations, but do not modify disease outcomes over time. Further, longitudinal studies in children to adulthood have shown that these treatments do not improve asthma severity or fixed airflow obstruction over time. In asthma, fixed airflow obstruction is caused by remodeling of the airway wall, but such airway remodeling also significantly contributes to airway closure during bronchoconstriction in acute asthmatic episodes. The goal of the current review is to understand what is known about the heterogeneity of airway remodeling in asthma and how this contributes to the disease process. We provide an overview of the existing knowledge on airway remodeling features observed in asthma, including loss of epithelial integrity, mucous cell metaplasia, extracellular matrix remodeling in both the airways and vessels, angiogenesis, and increased smooth muscle mass. While such studies have provided extensive knowledge on different aspects of airway remodeling, they have relied on biopsy sampling or pathological assessment of lungs from fatal asthma patients, which have limitations for understanding airway heterogeneity and the entire asthma syndrome. To further understand the heterogeneity of airway remodeling in asthma, we highlight the potential of in vivo imaging tools such as computed tomography and magnetic resonance imaging. Such volumetric imaging tools provide the opportunity to assess the heterogeneity of airway remodeling within the whole lung and have led to the novel identification of heterogenous gas trapping and mucus plugging as important predictors of patient outcomes. Lastly, we summarize the current knowledge of modification of airway remodeling with available asthma therapeutics to highlight the need for future studies that use in vivo imaging tools to assess airway remodeling outcomes. [ABSTRACT FROM AUTHOR]

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Asthma is a major driver of health care costs across ages. Despite widely disseminated asthma-treatment guidelines and a growing variety of effective therapeutic options, most patients still experience symptoms and/or refractoriness to standard of care treatments. As a result, most patients undergo a further intensification of therapy to optimize symptom control with a subsequent increased risk of side effects. Raising awareness about the relevance of evaluating aeroallergen sensitizations in asthmatic patients is a key step in better informing clinical practice while new molecular tools, such as the component resolved diagnosis, may be of help in refining the relationship between sensitization and therapeutic recommendations. In addition, patient care should benefit from reliable, easy-to-measure and clinically accessible biomarkers that are able to predict outcome and disease monitoring. To attain a personalized asthma management and to guide adequate treatment decisions, it is of paramount importance to expand clinicians' knowledge about the tangled relationship between asthma and allergy from a molecular perspective. Our review explores the relevance of allergen testing along the asthma patient's journey, with a special focus on recurrent wheezing children. Here, we also discuss the unresolved issues regarding currently available biomarkers and summarize the evidence supporting the eosinophil-derived neurotoxin as promising biomarker. [ABSTRACT FROM AUTHOR]

Introduction: Small airway dysfunction (SAD) commonly presents in patients with classic asthma, which is associated with airway inflammation, disease severity, and asthma control. However, the prevalence of SAD, its relationship with cough severity and airway inflammation, and its development after antiasthmatic treatment in patients with cough variant asthma (CVA) need to be clarified. This study aimed to investigate the prevalence of SAD and its relationship with clinical and pathophysiological characteristics in patients with CVA and the change in small airway function after antiasthmatic treatment. Methods: We retrospectively analyzed 120 corticosteroid-naïve patients with CVA who had finished a standard questionnaire and relevant tests in a specialist cough clinic, such as cough visual analog scale (VAS), differential cells in induced sputum, fractional exhaled nitric oxide (FeNO) measurement, spirometry, and airway hyper-responsiveness. Information of 1-year follow-up was recorded in a part of patients who received complete cough relief after 2 months of treatment. SAD was defined as any two parameters of maximal mid-expiratory flow (MMEF)% pred, forced expiratory flow at 50% of forced vital capacity (FEF50%) pred, and forced expiratory flow at 75% of forced vital capacity (FEF75%) pred measuring <65%. Results: SAD occurred in 73 (60.8%) patients with CVA before treatment. The patients with SAD showed a significantly longer cough duration (24.0 vs. 6.0, p = 0.031), a higher proportion of women (78.1 vs. 59.6%, p = 0.029), older mean age (41.9 vs. 35.4, p = 0.005), and significantly lower forced expiratory volume in 1 s (FEV1%) pred, FEV1/FVC, MMEF% pred, FEF50% pred, FEF75% pred, PEF% pred, and PD20 (all p < 0.01) as compared with patients without SAD. There were no significant differences in cough VAS, sputum eosinophils count, FeNO, and TIgE level between patients with SAD and those without SAD. Among 105 patients who completed 2 months of antiasthmatic treatment and repeatedly experienced spirometry measurement, 57 (54.3%) patients still had SAD, despite a significant improvement in cough VAS, sputum eosinophils, FeNO, FEF50% pred, and PEF% pred (all p < 0.01). As compared with patients without SAD, patients with SAD showed no significant differences in the relapse rate (50.0 vs. 41.9%, p = 0.483) and wheeze development rate (10.4 vs. 0%, p = 0.063) during the follow-up. Conclusions: Small airway dysfunction occurred in over half of patients with CVA and persisted after short-term antiasthmatic treatment, which showed distinctive clinical and pathophysiological features. [ABSTRACT FROM AUTHOR]

Asthma is one of the most common respiratory diseases encountered in clinical practice. Although the vast majority of asthmatics can be adequately controlled with inhaled steroids and other preventer medications, a small proportion remain uncontrolled. Anti-IgE treatment with omalizumab has been proposed in patients as a preferred approach in step 5 asthma therapy according to GINA guidelines. Although therapy with this molecule is approved for patients with atopic asthma and pretreatment serum IgE levels of 30-1500 only, there have been a few reports of its efficacy in subjects outside this reference IgE range. We report the case of a middle-aged lady with severe corticosteroid-dependent asthma and low serum IgE levels who was successfully treated with 9 months of omalizumab therapy. She gained good asthma control and was tapered off steroid use by the fifth month of therapy with omalizumab. The case report stresses the need for further investigation into expanding the spectrum of omalizumab usage in asthma beyond the current IgE suitability range. [ABSTRACT FROM AUTHOR]

Approximately 5–10% of asthmatic patients worldwide suffer from severe asthma. Experimental and clinical studies have demonstrated that IL-13 is an important cytokine in chronic airways inflammation. IL-13 is involved in Th2 inflammation and has been identified as a possible therapeutic target in the treatment of asthma. Two different human monoclonal antibodies (mAbs) anti-IL-13 (tralokinumab and lebrikizumab) block binding and signaling of IL-13 to its receptors, IL-13Rα1 and IL-13Rα2. Several randomized, double-blind, placebo-controlled multicenter studies have evaluated the safety and efficacy of tralokinumab and lebrikizumab in the treatment of adult patients with severe asthma, but all have failed to meet their primary endpoints. No serious adverse events related to the treatment with these anti-IL-13 mAbs have been reported in these studies. These negative clinical results contrast with positive findings from blocking IL-13 signaling in experimental models of asthma, raising doubts about the transferrable value of some models. Interestingly, dupilumab, a mAb which blocks both IL-4 and IL-13 signaling reduces exacerbation rates and improves lung function in severe asthmatics. These results suggest that IL-4 and IL-13 share some, but not all functional activities in airway inflammation. Tralokinumab might show efficacy in a highly selected cohort of asthmatics characterized by overexpression of IL-13. [ABSTRACT FROM AUTHOR]

Asthma is often associated with airway eosinophilia, and therapies targeting eosinophils are now available to treat severe eosinophilic asthma. Eosinophilic asthma is often due to a type-2 immune response and production of IL-5, which leads to eosinophilopiesis and recruitment of mature eosinophils in the airways. A concomitant type-2 and type-17 response has been reported in some individuals. IL-17 may be enhanced by IL-1β production and can lead to neutrophilic inflammation. In fact, both eosinophilic and neutrophilic (mixed granulocytic) inflammation are simultaneously present in a large population of patients with asthma. In monocyte/macrophage cell populations, release of mature IL-1β occurs via toll-like receptor ligand-induced activation of the inflammasome. Within the inflammasome, a cascade of events leads to the activation of caspase-1, which cleaves pro-IL-1β protein into a mature, releasable, and active form. We have demonstrated that eosinophils can release IL-1β in a Toll-like receptor ligand-independent fashion. The objective of this study was to determine the mechanisms underlying the production and maturation of IL-1β in cytokine-activated eosinophils. Using eosinophils from circulating blood and from bronchoalveolar lavage fluid after an airway allergen challenge, the present study demonstrates that cytokine-activated eosinophils express and release a bioactive form of IL-1β with an apparent size less than the typical 17 kDa mature form produced by macrophages. Using a zymography approach and pharmacological inhibitors, we identified matrix metalloproteinase-9 (MMP-9) as a protease that cleaves pro-IL-1β into a ~15 kDa form and allows the release of IL-1β from cytokine-activated eosinophils. Therefore, we conclude that activated eosinophils produce MMP-9, which causes the release of IL-1β in an inflammasome/caspase-1-independent manner. The production of IL-1β by eosinophils may be a link between the eosinophilic/type-2 immune response and the neutrophilic/type-17 immune response that is often associated with a more severe and treatment-refractory type of asthma. [ABSTRACT FROM AUTHOR]

The objective of the study was to evaluate the levels of IgE serum of Asthma patients as a parameter refer to hypersensitivy type 2 and correlation coefficient with some environmental factors. The present study was applied on 35of asthma patients and 15 healthy controls of same age and gender. Blood samples were collected from each patient as control and assessed by measurement of serum IgE (immunoglobulin) levels. In this project, the mean value of serum IgE in asthma patients was (585.41) IU/L. It was increased significantly compared to controls (148.95) IU/L. Also, it was increased significantly compared to controls (p = 0.001). Our findings demonstrated significant positive correlation between serum IgE and smoking levels (p=0.001). [ABSTRACT FROM AUTHOR]

The pathogenesis of asthma is complex and multi-faceted. Asthma patients have a diverse range of underlying dominant disease processes and pathways despite apparent similarities in clinical expression. Here, we present the current understanding of asthma pathogenesis. We discuss airway inflammation (both T2HIGH and T2LOW), airway hyperresponsiveness (AHR) and airways remodelling as four key factors in asthma pathogenesis, and also outline other contributory factors such as genetics and co-morbidities. Response to current asthma therapies also varies greatly, which is probably related to the inter-patient differences in pathogenesis. Here, we also summarize how our developing understanding of detailed pathological processes potentially translates into the targeted treatment options we require for optimal asthma management in the future. [ABSTRACT FROM AUTHOR]

Airway epithelial cells (AEC) exhibit a pro-inflammatory phenotype in patients with allergic asthma. We examined the effect of an allergic cytokine environment on the response of AEC to rhinovirus (RV), the most common trigger of acute exacerbations of asthma. Calu-3 cells, a well-differentiated human AEC line, were cultured with or without the T-helper type 2 cytokines interleukin (IL)-4 and IL-13, then stimulated with a toll-like receptor (TLR) 3 agonist (poly I:C, dsRNA) or a TLR7 agonist (imiquimod), or infected with RV 16. Expression of pro-inflammatory and antiviral mediators, and of viral pattern-recognition molecules, was assessed using nCounter assays, quantitative real-time PCR (qRT-PCR) and protein immunoassays. Both dsRNA and imiquimod stimulated expression of mRNA for IL6 and IL8 whereas expression of several chemokines and antiviral response genes was induced only by dsRNA. Conversely, expression of other cytokines and growth factors was induced only by imiquimod. RV infection not only stimulated expression of the inflammation-related genes induced by dsRNA, but also of complement factor B and the novel pro-inflammatory cytokine IL-32. In the T helper type 2 (Th2) cytokine environment, several mediators exhibited significantly enhanced expression, whereas expression of interferons was either unchanged or enhanced. The allergic environment also increased expression of pattern-recognition receptors and of intercellular adhesion molecule 1, the cell surface receptor for RV. We conclude that Th2 cytokines promote increased production of pro-inflammatory mediators by AEC following infection with RV. Increased viral entry or enhanced signalling via pattern-recognition receptors could also contribute to the exaggerated inflammatory response to RV observed in allergic asthmatics. [ABSTRACT FROM AUTHOR]

Asthma is a common childhood disease and several risk factors have been identified; however, the impact of genes and environment is not fully understood. The aim of the Swedish Twin study On Prediction and Prevention of Asthma (STOPPA) is to identify environmental (birth characteristics and early life) and genetic (including epigenetic) factors as determinants for asthmatic disease. Based on the Child and Adolescent Twin Study in Sweden (CATSS) (parental interview at 9 or 12 years, N ~23,900) and an asthma and/or wheezing algorithm, we identified a sample of monozygotic (MZ) and dizygotic (DZ) same-sexed twin pairs. The twin pairs were classified as asthma concordant (ACC), asthma discordant (ADC) and healthy concordant (HCC). A sample of 9- to 14-year-old twins and their parents were invited to participate in a clinical examination. Background characteristics were collected in questionnaires and obtained from the National Health Registers. A clinical examination was performed to test lung function and capacity (spirometry with reversibility test and exhaled nitric oxide) and collect blood (serology and DNA), urine (metabolites), feces (microbiota), and saliva (cortisol). In total, 376 twin pairs (752 individual twins) completed the study, response rate 52%. All participating twins answered the questionnaire and >90% participated in lung function testing, blood-, and saliva sampling. This article describes the design, recruitment, data collection, measures, and background characteristics, as well as ongoing and planned analyses in STOPPA. Potential gains of the study include the identification of biomarkers, the emergence of candidates for drug development, and new leads for prevention of asthma and allergic disease. [ABSTRACT FROM AUTHOR]

Respiratory muscle weakness is a common feature of a multitude of cardiopulmonary diseases and has led to an increasing awareness that respiratory muscle weakness can be a compounding factor in many diseases associated with higher morbidity and mortality. The aim of the study was to ascertain the effect of breathing and aerobic training on manual volitional respiratory muscle strength and function in moderate, persistent asthmatics. Eighty-eight previously sedentary, moderate, persistent asthmatics were divided into either a non-exercising control (NON), endurance trained (ET), inspiratory and expiratory trained (IEB) or endurance trained combined with inspiratory and expiratory trained (COM) group. The exercise groups trained three times weekly over an eight-week period. The ET programme (n = 22) consisted of walking/jogging at 60% of individual age-predicted maximum heart rate, the IEB programme (n = 22) of inspiratory and expiratory training in a semi-recumbent position at varying inspiration, expiration ratios while the COM programme (n = 22) employed a combination of the ET and IEB programmes. The NON (n = 22) received no prescribed exercise and were instructed to continue their usual activities. ET, IEB and COM resulted in significant (p = 0.05) strength improvements in eleven of the thirteen measured inspiratory muscles. ET and COM resulted in significant strength improvements in all seven of the measured expiratory muscles, while IEB improved the strength of five of the seven measured expiratory muscles, excluding left lattisimus dorsi and left quadratus lumborum. There were no significant changes in any of the measured variables in the NON group. Increases in respiratory muscle strength as a result of exercise training are essential to the patient to ensure ventilation by adapting to the increasing workloads associated with the disease. In addition, having multiple or alternative tests of respiratory muscle function available both increases diagnostic precision and makes assessment and follow-up possible in a range of clinical circumstances. [ABSTRACT FROM AUTHOR]

In asthmatic patients, inhalation of hyperosmolar saline or D-mannitol (D-M) elicits bronchoconstriction, but in healthy subjects exercise causes bronchodilation. Hyperventilation causes drying of airway surface liquid (ASL) and increases its osmolarity. Hyperosmolar challenge of airway epithelium releases epithelium-derived relaxing factor (EpDRF), which relaxes the airway smooth muscle. This pathway could be involved in exercise-induced bronchodilation. Little is known of ASL hyperosmolarity effects on epithelial function. We investigated the effects of osmolar challenge maneuvers on dispersed and adherent guinea-pig tracheal epithelial cells to examine the hypothesis that EpDRF-mediated relaxation is associated with epithelial cell shrinkage. Enzymatically-dispersed cells shrank when challenged with ⩾10 mOsM added D-M, urea or NaCl with a concentration-dependence that mimics relaxation of the of isolated perfused tracheas (IPT). Cells shrank when incubated in isosmolar N-methyl-D-glucamine (NMDG) chloride, Na gluconate (Glu), NMDG-Glu, K-Glu and K2SO4, and swelled in isosmolar KBr and KCl. However, isosmolar challenge is not a strong stimulus of relaxation in IPTs. In previous studies amiloride and 4,4'-diisothiocyano-2,2'-stilbenedisulfonic acid (DIDS) inhibited relaxation of IPT to hyperosmolar challenge, but had little effect on shrinkage of dispersed cells. Confocal microscopy in tracheal segments showed that adherent epithelium is refractory to low hyperosmolar concentrations that induce dispersed cell shrinkage and relaxation of IPT. Except for gadolinium and erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA), actin and microtubule inhibitors and membrane permeabilizing agents did not affect on ion transport by adherent epithelium or shrinkage responses of dispersed cells. Our studies dissociate relaxation of IPT from cell shrinkage after hyperosmolar challenge of airway epithelium. [ABSTRACT FROM AUTHOR]

Hyperventilation-induced hypocapnia is common among asthma patients. This case study illustrates both methodology and results from a patient undergoing training in capnometry-assisted respiratory training (CART). CART is a 4-week training aimed at normalizing basal and acute levels of end-tidal carbon dioxide (PCO) using a portable capnometer. In the presented case, basal levels of PCO increased from hypocapnic to normocapnic range over the course of treatment. Improvements were accompanied by improvements in lung function and reductions in diurnal lung function variability. Improvements remained stable throughout follow-up. [ABSTRACT FROM AUTHOR]

Asthma is characterized by airflow obstruction that is usually completely reversible either spontaneously or in response to treatment. However, a small subset of patients with asthma display FAO (fixed airflow obstruction) despite optimal treatment, a feature more commonly associated with smoking-induced COPD (chronic obstructive pulmonary disease). Why some asthma patients develop FAO is not understood, and it is not clear whether (i) they represent a subset of patients with more severe disease, (ii) they share some characteristics of patients who develop COPD, or (iii) they represent a different disease entity altogether. The present review compares the pulmonary inflammatory profile of asthma patients with FAO with those without FAO, as well as COPD sufferers. The inflammation in asthma patients with FAO can vary from neutrophilic with CD8 T-cell involvement, similar to that of COPD, to eosinophilic with CD4 Th2 cell involvement, akin to that of asthma patients without FAO. Although studies of FAO in asthma sufferers would benefit hugely from consistent inclusion criteria, further research work is also required to shed more light on the immunological processes involved. [ABSTRACT FROM AUTHOR]

Tissue factor (TF) is important for initiation of coagulation and for the increased thrombin activity observed at sites of inflammation. Thrombin activity is induced by allergen challenge in asthmatic airways and is involved in the pathogenesis of asthma. A −603A → G polymorphism (rs1361600) in the promoter region of the TF gene has been associated with serum TF levels and with the development of cardiovascular diseases. The aim of this study was to determine whether the functional −603A → G polymorphism has genetic influences on the development of asthma. Case–control analysis was performed of the association between six common single-nucleotide polymorphisms (SNPs), including the −603A → G polymorphism, at the TF gene, and the development of asthma, using two unrelated Japanese populations. In the primary population (n=826), the GG genotype at the −603A → G polymorphism was associated with adult-onset asthma (onset at 21 years of age) (odds ratio (OR) 2.886, P=0.0231). A second population showed a similar tendency (n=1654, OR 1.602, P=0.064). Transcriptional activity of promoters with −603A → G genotypes were examined using luciferase promoter assays. The −603G allele was associated with higher promoter activity (P<0.05). The association between the functional polymorphism (−603A → G) in the TF gene promoter and adult-onset asthma indicates that TF is a candidate gene contributing to asthma susceptibility. [ABSTRACT FROM AUTHOR]

Objective. Bronchial hyperresponsiveness is usually measured by bronchial challenge with direct (e.g. methacholine) and indirect (e.g. adenosine) agonists. A prospective, randomized, crossover, single-blind study was performed to compare both methods in the first diagnosis of asthma. Patients and methods. Fifty-seven patients, in which asthma was suspected, were selected (21 male, 36 female). Fifty-four underwent both challenges following the five-breath dosimeter protocol. PC20 was calculated according to ATS guidelines. Data of symptoms developed during the challenge, PC20 methacholine and adenosine, and FEV1 improvement after bronchodilator therapy were recorded. Results. Symptoms at consultation were consistent with asthma in 68.4% patients, asthma and rhinitis in 29.8% and exercise-induced asthma in 1.8%. Atopy was reported in 93%; 49.1% had family history of atopy and 26.3% of asthma. The most frequent symptoms developed during the challenge were cough (40.4% with adenosine and 20.4% with methacholine) and wheezing (26.3% and 7.4% respectively), statistically significant differences. Bronchial challenge with MCh resulted positive in 44.4% of the patients and positive with AMP in 50%. Every patient with negative result to adenosine, was also negative to methacholine. In 94.4% subjects the result of both challenges was concordant (kappa index = 0.889). PC20 in both challenges showed poor linear correlation (Pearson r = 0.43, p < 0.05). Positivity of both challenges was only associated with having a positive skin prick test to danders (p = 0.001). Percentage of improvement after bronchodilator was 34.9% (SD12.2%) with adenosine challenge and 33.9% (SD17.9%) with methacholine (differences non statistically significant). Conclusions. Concordance in the result of both techniques is very high. Cough and wheezing are more frequent with adenosine, though not severe. PC20 with both techniques shows poor linear correlation. [ABSTRACT FROM AUTHOR]

Background. Various factors have been reported to be useful for predicting future exacerbations. Objective. This study was intended to determine a usefulness of a combination of a patient-based questionnaire, such as the Asthma Control Test (ACT) score with objective assessments, such as forced expiratory volume in 1 second (FEV1) and/or exhaled nitric oxide (FENO), for predicting future exacerbations in adult asthmatics. Methods. We therefore enrolled 78 subjects with mild to moderate asthma, who were clinically stable for 3 months who all had been regularly receiving inhaled steroid treatment. All subjects underwent a routine assessment of asthma control including the ACT score, spirometry, and FENO, and then were followed up until a severe exacerbation occurred. The predictors of an increased risk of severe exacerbation were identified and validated using decision trees based on a classification and regression tree (CART) analysis. The properties of the developed models were the evaluated with the area under the ROC curve (AUC) (95% confidence interval [CI]). Results. The CART analysis automatically selected the variables and cut-off points, the ACT score ≤23 and FEV1 ≤ 91.8%, with the greatest capacity for discriminating future exacerbations within one year or not. When the probalility was calculated by the likelihood ratio of a positive test (LP), the ACT score ≤23 was identified with a 60.3% probability, calculated by 1.82 of LP, whereas the combined ACT score ≤23 and the percentage of predicted FEV1 ≤ 91.8% were identified with an 85.0% probability, calculated by an LP score of 5.43, for predicting future exacerbation. Conclusion. These results demonstrated that combining the ACT score and percentage of predicted FEV1, but not FENO, can sufficiently stratify the risk for future exacerbations within one year. [ABSTRACT FROM AUTHOR]

Background. Inhaled corticosteroids (ICS) are used in asthma therapy for their anti-inflammatory effects. P-glycoprotein (PGP) is a transmembrane efflux pump for many drugs, including corticosteroids. Expression of PGP is associated with therapy resistant disease. Objective. The purpose of this study was to compare expression levels of PGP in blood lymphocytes of pediatric asthma patients either on ICS or on the leukotriene inhibitor montelukast medication. Patients and Methods. The evaluation of lymphocyte PGP expression was performed on a sample of 99 children (66 boys and 33 girls) aged 2-18 (median 12) years with intermittent or persisting mild asthma, (as defined by GINY 2002). The asthmatic children were divided into 3 groups: (1) treated by ICS budesonide 200-400 μg per day (n = 27) more than 1 year; (2) treated by oral montelukast 4 or 5 mg at an age-based dose (n = 16); and (3) treated by inhaled corticosteroids and montelukast (n = 45). Reference PGP values were obtained from a group of 64 healthy children (23 boys and 29 girls) aged 2-15 years (median, 10 years). The expression of lymphocyte PGP was determined on fixed and permeabilized blood mononuclear cells using indirect immunofluorescence staining technique by flow cytometry modified according to Boer et al., 1997. Results. Based on the weighted medians for PGP expression in peripheral blood lymphocytes, we found a significant difference (p < 10-3) between the group of asthma patients (n = 99), (619 ± 5.3) and healthy controls (n = 64) (446.9 ± 4.4). Second, there was a lower level of PGP expression in the group treated by ICS (548.6 ± 9) than the group treated by montelukast and montelukast with budesonide (643.2 ± 6.3) (p < 10-6). Conclusions. The anti-inflammatory activity of ICS is more effective in decreasing the production of pro-inflammatory mediators and results in reduced multidrug resistence (MDR-1) gene activity and expression of lymphocyte PGP in asthmatic children. [ABSTRACT FROM AUTHOR]

Adenosine monophosphate (AMP) challenge is a diagnostic tool for asthma. The aim of this study is to evaluate the effect of low dose inhaled budesonide (IB) on PC20AMP levels. Seventeen stable mild asthmatic patients were prospectively recruited. After initial testing, patients were administered 400 μ g of inhaled budesonide. AMP challenge was then repeated at the 12th hour and 5th,15th, 30th, and 90th days of the treatment. AMP challenge resulted in negative in 47% of the patients at 12-hour testing. This study suggests that low-dose IB may return airway responsiveness as early as 12 hours and AMP challenge may be effectively used for treatment monitorization. [ABSTRACT FROM AUTHOR]

There are a number of useful direct airway sampling procedures to help diagnose and monitor asthma in patients. However, non-invasive techniques are the ideal, especially in children, given the necessity of safe and repeatable measurements to monitor treatment efficacy and disease progression. Bronchoalveolar lavage (BAL) may be too invasive for clinical use in children, while questions still surround the utility of induced sputum (IS). More novel techniques, such as fractional exhaled nitric oxide (FENO) and exhaled breath condensate (EBC), are still unproven. Eosinophilic airway inflammation is a major feature of childhood asthma, and it has been revealed as a major treatment target with inhaled corticosteroids. Moreover, treatment protocols governed by sputum eosinophil counts may be more efficacious - by reducing the frequency and severity of exacerbations - than treatment based on clinical symptoms and other traditional objective measures of lung function. The selection of an appropriate airway inflammation monitoring technique must take everything into consideration, including safety, reproducibility, repeatability, sensitivity to treatment, and the overall clinical/research goals. [ABSTRACT FROM AUTHOR]

Rationale. Negative affectivity is a measure of anxiety associated with increased reporting of symptoms. Few studies have explored this association with respect to drug-induced symptoms in patients taking medication for a chronic disease in real life. Objectives. In this cross-sectional study we examined the relationship between negative affectivity and self-reported side effects of inhaled corticosteroids in patients with asthma. We also investigated differential associations due to side effect type (subjective versus observable side effects) and treatment impact (i.e., hierarchical dosing). Methods. A total of 228 asthma patients, taking inhaled corticosteroids, completed scales measuring inhaled corticosteroid-induced side effects (Inhaled Corticosteroid Questionnaire scored: 0 = none; 100 = worst) and negative affectivity (Positive and Negative Affect Schedule scored: 10-50). Patients were grouped into low, average, and high negative affectivity groups based on published norms. Results. Patients high in negative affectivity reported significantly greater (p < 0.001) side effects (median score 20.5 (IQR: 11.4-33.0) than the groups of patients scoring lower on this measure (low negative affectivity: 7.1 (3.1-15.6); average: 13.3 (4.9-23.3)). The relationship between negative affectivity and side effects was stronger among patients taking low (r = 0.40-0.45) rather than mid to high inhaled corticosteroid doses (r = 0.16-0.28). Conclusions. Asthma patients with higher negative affectivity using inhaled corticosteroids report increased medication-induced symptoms. Clinicians should be aware that aside from inhaled corticosteroid dosage, the personality of the patient is an important factor in the reporting of drug-related side effects. [ABSTRACT FROM AUTHOR]

Background and aim: Asthma is a variable disease, and therapy should be tailored accordingly. The aim of this study was to explore patterns of self-management in response to disease variability in adult asthmatics. Methods: Adult asthmatics (n = 509), recruited through a web-based panel, answered a questionnaire concerning asthma knowledge, compliance, and treatment, including specified treatment options, through the Internet. Results: Two-thirds of the patients on inhaled corticosteroids (ICS) stepped-up and down their daily dose without prior contact to their doctor, and more than 50% took less ICS than prescribed during periods with fewer symptoms. In case of deterioration, 57% of the patients would only increase their reliever medication, whereas 23% would also increase their controller medication, although 59% were instructed by their doctor to do so. The self-perceived severity of asthma (graded as mild, moderate or severe) was not associated with the patients' response pattern. The preferred treatment strategy, differing primarily with regard to dosing and timing of controller medication, was associated with feeling safe about self-adjustment of controller medication (p < 0.001), but not with self-reported knowledge of asthma (p > 0.5). Conclusion: In case of deterioration, the majority of adult asthmatics only increase their reliever medication, although instructed by their doctors also to increase their controller medication. Furthermore, the patients' preferred strategy for management of disease variability seems not to be driven by their knowledge of the disease. [ABSTRACT FROM AUTHOR]

Background: Inhaled corticosteroids (ICSs) are the most effective anti-inflammatory drugs for adult asthma and can improve not only clinical symptoms but also bronchial hyperresponsiveness (BHR). However, the prognosis of adult asthma has not been well studied, and it remains to be elucidated precisely how long treatment with ICSs should be continued once clinical remission is achieved. Objectives: We examined whether ICS use could be withdrawn or reduced without exacerbation of disease. Methods: We retrospectively studied 374 adult patients with asthma to determine which factors predicted the elimination or reduction of ICS treatment without exacerbations of disease after the achievement of normalized BHR to acetylcholine. The patients were classified into three groups: Group 1 had symptoms within 6 months of normalization and needed to continue therapy; group 2 received the equivalent of ≥ 400 μ g fluticasone propionate until BHR normalization, did not have symptoms in the 6 months after normalization, and then had their doses of ICSs halved; and group 3 received the equivalent of ≤ 200 μ g fluticasone propionate at an enrollment, did not have symptoms in the 6 months after normalization, and then had all ICSs withdrawn. The primary outcome measure was the presence of clinical symptoms. We used multiple logistic regression and a Kaplan-Meier analysis to analyze the factors predicting remission. Results: Twenty-nine patients in group 3 remained asymptomatic for more than 30 months (mean 47.1 ± 12.4 months) after discontinuing ICS therapy. The predictive markers of remission were low levels of eosinophils in the sputum, high %V50 at the first hospital visit, and the need for only a low daily dose of ICS to induce normalized BHR. Conversely, patients with severe BHR at the first hospital visit, low %FEV1 at normalized BHR, and a need for high-dose ICSs to reach normalized BHR could not reduce or discontinue treatments. Conclusion: Some adult patients with asthma whose BHR is normalized by ICS therapy can achieve remission from disease exacerbation after discontinuation of ICSs. However, patients with severe asthma or asthma of long duration may not achieve remission even if their BHR is normalized. [ABSTRACT FROM AUTHOR]

Knowing about spontaneous variations in the fractional concentration of exhaled nitric oxide (FENO) could improve monitoring of airway inflammation in asthmatic children. We aimed to assess FENO variations (expiratory flow 50 mL/sec) in subjects maintained in similar environmental conditions. We tested spirometry and FENO in symptom-free asthmatic children (9 corticosteroid-naive, 8 corticosteroid-treated) during a 1-week stay in a countryside sanatorium and in their healthy relatives (n = 12) staying in the immediate neighborhood on summer holiday (total 29 children, M/F:14/15, 5.8-16.8 yrs). Testing sessions were repeated every 12 hours (8:00 am, 8:00 pm) for 2 days and again on day 7. Measurements were defined as reproducible when they agreed with an intraclass correlation coefficient (ICC) above 0.60; deviation from mean differences was assessed by the coefficient of repeatability (CR = 2 SD). Lung function remained constant throughout the week in all groups. Baseline FENO levels in corticosteroid-naive asthmatic children tended to decrease at the end of the week (from 13.9 ppb, 95% CI 12.2-19.1 to 9.2 ppb, 95% CI 5.8-15.9, p = 0.057). No differences were found between nocturnal and diurnal FENO. Within-session reproducibility for two FENO measurements was high (ICC 0.99 in all groups and CR, 0.9 to 1.3 ppb). Between-session FENO reproducibility at 12 hours and 24 hours was still high for each group but decreased markedly after 6 days in corticosteroid-naive asthmatic children (ICC 0.79 and CR 9.6 ppb at 24 hours vs. ICC 0.13 and CR 20.8 ppb after 6 days), whereas it decreased slightly in corticosteroid-treated asthmatics (from ICC 0.89 and CR 3.1 ppb to ICC 0.88 and CR 3.0 ppb) and healthy children (from ICC 0.79 and CR 4.8 ppb to ICC 0.65 and CR 5.7 ppb). In conclusion, in healthy subjects and in asthmatic children receiving therapy with inhaled corticosteroids (but not in corticosteroid-naive subjects), FENO measurements are reproducible across a week. [ABSTRACT FROM AUTHOR]

A goal of asthma management is to improve the patient’s health-related quality of life (HRQL). However, it is unclear whether HRQL instruments can discriminate across asthma control measures. The objective of this study was to evaluate the validity of generic and condition-specific preference-based instruments, in terms of their ability to distinguish asthma control. Asthma patients ( n = 157) completed three generic preference-based instruments: the Health Utility Index Mark 3 (HUI-3), the EuroQol (EQ-5D), and the Short Form 6D (SF-6D) and two condition-specific questionnaires: the standardized Asthma Quality of Life Questionnaire (AQLQ(S)) and the Asthma Control Questionnaire (ACQ). The AQLQ(S) scores were converted into the condition-specific preference-based scores: the Asthma Quality of Life Utility Index (AQL-5D). The preference-based instruments were generally able to discriminate across control measures, such as ACQ scores and magnitude of asthma medication, but were not able to discriminate for self-reported control and severity levels. These instruments also correlated with most control measures ( r = 0.32–0.37). Significant relationships between AQL-5D scores and all control variables were observed. Overall, the AQL-5D discriminated across all levels of asthma control. The HUI-3, the EQ-5D, and the SF-6D differentiated between the highest and lowest levels of control but could not discriminate between the moderate levels. [ABSTRACT FROM AUTHOR]

Rationale and aims Quality circles (QCs) are well established as a means of aiding doctors. New quality improvement strategies include benchmarking activities. The aim of this paper was to evaluate the efficacy of QCs for asthma care working either with general feedback or with an open benchmark. Methods Twelve QCs, involving 96 general practitioners, were organized in a randomized controlled trial. Six worked with traditional anonymous feedback and six with an open benchmark; both had guided discussion from a trained moderator. Forty-three primary care practices agreed to give out questionnaires to patients to evaluate the efficacy of QCs. Results A total of 256 patients participated in the survey, of whom 185 (72.3%) responded to the follow-up 1 year later. Use of inhaled steroids at baseline was high (69%) and self-management low (asthma education 27%, individual emergency plan 8%, and peak flow meter at home 21%). Guideline adherence in drug treatment increased ( P = 0.19), and asthma steps improved ( P = 0.02). Delivery of individual emergency plans increased ( P = 0.008), and unscheduled emergency visits decreased ( P = 0.064). There was no change in asthma education and peak flow meter usage. High medication guideline adherence was associated with reduced emergency visits (OR 0.24; 95% CI 0.07–0.89). Use of theophylline was associated with hospitalization (OR 7.1; 95% CI 1.5–34.3) and emergency visits (OR 4.9; 95% CI 1.6–14.7). There was no difference between traditional and benchmarking QCs. Conclusions Quality circles working with individualized feedback are effective at improving asthma care. The trial may have been underpowered to detect specific benchmarking effects. Further research is necessary to evaluate strategies for improving the self-management of asthma patients. [ABSTRACT FROM AUTHOR]

Objective. This pilot study explores the reported symptoms in African Americans and Caucasians with asthma. Methods. Asthma patients in an inner-city pulmonary clinic were given a brief questionnaire of asthma symptoms and the BORG scale, followed by spirometry. Results. African Americans were less likely to report nocturnal awakenings (67% vs. 100%; p = 0.037), complain of dyspnea (33% vs. 75%; p = 0.038), or experience chest pain (13% vs. 75%; p = 0.002) than Caucasians. Conclusions. This is the first study to demonstrate that there are clinically significant differences in the reporting of asthma symptoms between African Americans and Caucasians. [ABSTRACT FROM AUTHOR]

Purpose: To quantify the association between cardiovascular disease (CVD) and asthma in Canadian adults and to determine whether age of asthma onset is a moderator of this association. Methods: We used a sample of 74 342 participants with a mean age of 56.4 ± 12.5 from cycle 1.1 of the Canadian Community Health Survey. Asthma age of onset was categorized into early-onset (0-20 years) and adult-onset (21-54 years). Three major outcomes were used to estimate the relationship between asthma and CVD, namely: high blood pressure, heart disease, and stroke. Results: Multiple logistic regression models revealed that asthmatics were 43% (OR = 1.43, CI = 1.19-1.72) more likely to have heart disease, and 36% (OR = 1.36, CI = 1.21-1.53) more likely to have high blood pressure than non-asthmatics. There were no consistent results for age of onset with high blood pressure, heart disease, or stroke. Conclusion: Using a population-based dataset we confirmed that asthmatics are at increased odds of cardiovascular disease compared to non-asthmatics; furthermore, age of asthma onset did not appear to moderate this relationship. Future research should focus on determining whether asthma severity or allergic/non-allergic phenotypes have a differential effect on the asthma-CVD relationship. [ABSTRACT FROM AUTHOR]

This prospective exploratory story examined diurnal variations in pulmonary function and their association with sleep and quality of life (QOL) in 20 adult asthmatics. Peak expiratory flow (PEF) was assessed for 7 days, before bedtime and upon awakening. There was no association between PEF variability and QOL. Six of 13 polysomnographic measures were significantly correlated with overnight decline in PEF. Individuals with greatest decline took longer to fall asleep and enter Stage 1 sleep, spent less time asleep, and experienced poorer sleep efficiency. Diurnal variations in PEF reflect adverse sleep quality, yet impact on QOL is often unnoticed. [ABSTRACT FROM AUTHOR]

Self-reported symptoms, FEV1, and clinician judgment are all used to evaluate asthma control. The relative utility of each measure of control cannot be easily assessed. Item response theory (IRT) approaches allow for the direct comparison of the utility of different types of measures used to assess control. The objective of this study was to evaluate the validity and reliability of evaluating asthma control using symptom, clinical, and physiologic measures by applying an IRT approach. Subjects receiving care at an asthma clinic were evaluated on measures of asthma control. Based on 114 evaluations, IRT parameters were estimated to evaluate whether measures assessed a single underlying construct, the hierarchical relationship between the measures and the level of control each measure assessed, whether measures targeted all levels of asthma control, and whether the scoring categories distinguished between different levels of control. Infit statistics (0.74-1.5) for individual items showed that all items fit the underlying concept of asthma control. The reproducibility of the hierarchal scale was high (0.9). The results also demonstrated that items differentiated two strata (high, low) of control. The gaps in the hierarchal scale showed that for many subjects (37%) there were no items at their level of asthma control. The IRT approach identified gaps in current measurement that need to be addressed to provide more precise evaluations of control required to accurately monitor changes in patient status. [ABSTRACT FROM AUTHOR]

The aim of this study was to validate the QUOTAC, a questionnaire on day and night time respiratory symptoms in asthmatic children. Validity was examined by measuring agreement between the QUOTAC and a self-report diary in children aged 6 to 16 years, divided in an asthma group and a control group. As an extra interest in our study a sum score was computed as a measure of the severity of asthma. This study shows that the QUOTAC is discriminative between asthmatic and healthy children and is a reliable and sensitive scale for measuring the severity of asthma. However, cut-off scores for mild, moderate, or severe asthma should be investigated in further research. [ABSTRACT FROM AUTHOR]

Exercises testing and cold air challenges are frequently used to assess airway hyperresponsiveness (AHR), but different goals are set for the two tests. We, therefore, wished to determine whether cold air and exercise challenge testing yielded similar responses and if any differences were due to differences in the maximum minute ventilation achieved. Twenty asthmatic subjects each performed a cold air (CACh) and an exercise (EXCh) challenge. Baseline forced expiratory volume in one second (FEV1) was recorded immediately pre-challenge and then serially for at least 10 minutes post-challenge. The maximum minute ventilation achieved was recorded. In the subjects who had at least a decrease in FEV1 of 15% in response to the first CACh, a second CACh was performed, but at the maximum minute ventilation achieved during EXCh. Eleven subjects after CACh and four after EXCh had a greater than 15% decrease in FEV1 (p = 0.05). The median decrease in FEV1 was greater following the CACh (16.7%[25th to 75th percentile 10.4 to 19.9]) than the EXCh (6.9%[25th to 75th percentile 4.3 to 14.6]); (p = 0.0004). The median maximum minute ventilation achieved was greater with the CACh (89[66-141] L/min) than with the EXCh (61(40 to 102)L/min); (p < 0.0001). Only one of seven subjects who had previously responded to the CACh had a 15% decrease in FEV1 when the CACh was repeated at the same maximum minute ventilation achieved during EXCh (p = 0.007). In conclusion, cold air and exercise challenges do not produce the same response. Our results highlight than an explanation is the differences in the maximum-minimum ventilation achieved. [ABSTRACT FROM AUTHOR]

The article discusses about airway hyperresponsiveness as a determinant of the early asthmatic response to inhaled allergen. It informs that seasonal allergic rhinitis and asthma are initially referred incorrectly as rose catarrh less than 200 years ago. To address this problem, Charles Harrison Blackley clarified that pollen is one cause of allergic airway symptoms, studies were conducted on allergen skin testing, allergen injection therapy and passive transfer of sensitization by serum.

Objective . To evaluate the prevalence of nocturnal symptoms in a large sample of asthmatic patients, and to assess the agreement between patients' complaints and general practitioners' (GPs') reports in primary care. Design . Cross-sectional survey involved 3,526 GPs and 751 specialists (pulmonologists and allergists) and included 13,493 patients with persistent asthma. Symptoms, treatment, and social and medical data were collected in real time by the patients and their GPs. Setting . France. Results . Prevalence of nocturnal symptoms was 60%. A total of 7,989 patients with nocturnal symptoms had complete data for both patients and GPs; 3,849 (48.1%) had perfect agreement between GP and their complaints for nocturnal symptoms (agreement group; [kappa = 1]); 3,376(42.2%) declared having no symptoms during the night, but these were detected by the GP during the visit (underestimated by patients and detected by GPs); 773(9.6%) declared having nocturnal symptoms, but these were not detected by GPs. Patients with a good agreement with their GP's opinion were significantly more frequently followed-up by a specialist than other patients ( p = 0.002). Conclusions . Nocturnal symptoms appear to be underdeclared by patients. GPs should therefore systematically ask their patients about nocturnal symptoms to increase control of asthma and to adequately manage its treatment. [ABSTRACT FROM AUTHOR]

Nonspecific hyperresponsiveness to adenosine monophosphate is better related to airway inflammation than methacholine. Adenosine induces mast cells and other cells to release inflammatory mediators that produce bronchoconstriction and perhaps other inflammatory effects, such as plasma exudation, which have not been well studied. We compared the plasma exudation effect, as measured in induced sputum, between adenosine and methacholine challenge in healthy and asthmatic subjects. In a cross-over design, 42 subjects were randomly challenged with adenosine or methacholine. After recovery, induced sputum was collected on 2 separate days, 48 to 72 hours apart. In the control group, an additional challenge with saline was performed. Differential cell counts and albumin and alpha2-macroglobulin levels were determined. The sputum volume obtained was sufficient to measure proteins in only 34 subjects: 10 healthy individuals and 24 mild asthmatics. There was a significant difference between adenosine and methacholine in sputum albumin (mean differences: 68[73.4] μg/L in controls, p = 0.039 and 48.0[162.9] μg/L in asthmatics) and cell counts, but only a tendency in alpha2-macroglobulin. PC20 adenosine was better related to eosinophil counts than methacholine ( r = -0.44, p = 0.014). Albumin or alpha2-macroglubulin levels were not significantly correlated with baseline FEV 1 , PC20, or eosinophil counts. Adenosine, but not methacholine challenge, produces a mild airway plasma exudation that does not seem to be relevant to bronchoconstriction. However, this could be relevant, to some supernatant measurements after adenosine challenge. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate which factors are associated with asthma control experienced by asthma patients. In a cross-sectional study patients aged 16–60 years with mild to moderate asthma were selected. The influence of the following factors on asthma control was studied in a multivariate model: age, gender, socioeconomic status, smoking, perceived hyperresponsiveness (PHR, responding with asthma symptoms to one or more triggers), allergy (Phadiatop®), long-acting bronchodilating agents, and inhaled corticosteroids. Asthma control was measured by means of the Asthma Control Questionnaire© (ACQ) as developed by Juniper. Forced expiratory volume in 1 second (FEV 1 ) was measured by means of a portable spirometer. In this study with 311 patients, mean ACQ score was 1.39 (range 0–4.43). A stepwise backward linear regression analysis showed that low socioeconomic status (beta 0.425; p = 0.001), current smoking (beta 0.555; p [ABSTRACT FROM AUTHOR]

Background. Objective assessment of airway function is important in epidemiologic studies of asthma to facilitate comparison between studies. Airway hyperresponsiveness (AHR), peak expiratory flow (PEF) variability, and bronchodilator reversibility (BR) are widely used as markers of airway lability in such studies. Data from a survey of a population sample of adolescents and young adults (n = 609; 288 males), aged 13–23 years, were analyzed to investigate whether AHR, PEF variability, and BR can be used interchangeably as markers of asthma in an epidemiological setting. Methods. Case history, including self-reported and doctor-diagnosed asthma, smoking habits, and use of asthma medication, was obtained by interview and questionnaire. Lung function, airway responsiveness (positive test: PC 20 FEV 1 20%), BR (positive test: ΔFEV 1 [(FEV 1 max - FEV 1 min)/FEV 1 max) 100]> 10%), blood eosinophil count, and skin prick test reactivity were measured by using standard techniques. Results. The prevalence of a positive test was AHR 16.4%, PEFpos 13.3%, and BRpos 7.2%, respectively; 73.5% of the sample had three negative tests. Among the 74 participants with current self-reported asthma (12.2%), 34 subjects (46%) had more than one positive test. Using AHR as the only objective marker of asthma identified 93% of the participants with current asthma, whereas PEF and BR identified 45% and 10%, respectively. Confining the analysis to participants with only one positive test revealed that 61% of the subjects with isolated AHR had current asthma, whereas none of the subjects with isolated BRpos had asthma, and only one participant with isolated PEFpos had current asthma. Degree of histamine responsiveness was closer associated with other asthma-related factors, including self-reported asthma, use of asthma medication, and level of lung function, than PEF variability and bronchodilator responsiveness. Conclusions. Airway responsiveness to histamine, diurnal peak-flow variability, and bronchodilator reversibility cannot be used interchangeably as objective markers of asthma in epidemiologic studies. On the basis of the present findings, airway hyperresponsiveness to a nonspecific bronchoconstrictor is recommended as the objective marker of asthma-related airway lability. [ABSTRACT FROM AUTHOR]

Background. Asthma is a complex inflammatory lung disease that results from allergic and nonallergic environmental exposures in genetically susceptible individuals. The interrelationship and impact of environmental and genetic determinants on the development of asthma is still unclear. Monozygotic twins (MZT) have been considered a potentially useful population to investigate the role of genetic and environmental factors on asthma because of their identical genetic background, similar childhood environmental exposures, and expected high concordance rate for asthma. Methods. A detailed questionnaire designed to obtain demographic information, medical history/severity of asthma, and environmental exposures was distributed to 43 pairs of MZT pairs where one or both probands had a history of asthma. All twin pairs were clinically evaluated for atopy by skin testing. Asthma was assessed by questionnaire, baseline spirometry, disease severity, airway reactivity, and medication scores. Results. Based on a history of physician-diagnosed asthma, disease severity, airway reactivity, and medication scores, 22 MZT pairs were identified as concordant (C) for asthma while 21 MZT pairs were discordant (D) for asthma. Those MZT-C for asthma were on average older and more often female. Adjusted odds ratios for age and gender revealed that MZT-C for asthma had a 2.3 greater likelihood of childhood tobacco exposure and a 1.8 greater likelihood of early exposure to a pet compared to MZT-D pairs. In addition, MZT-C for asthma had a 2.4 greater likelihood of being full term vs. premature at birth. None of these odds ratios were statistically significant due to a small sample size. However, a trend for a greater likelihood of earlier environmental exposures was observed for MZT-C asthma pairs. Among MZT-D probands, a history of asthma in one proband was supported by a lower FEV 1 and higher airway reactivity, disease severity, asthma symptom, and medication scores compared to the nonasthma proband. There was significant intrapair heterogeneity among MZT-C and MZT-D probands in their positive skin test responses to specific aeroallergens. Conclusion. Cross-sectional evaluation of larger MZT populations where one or both proband has asthma with a long-term prospective follow-up may be a feasible way for identifying the impact of environmental determinants as independent risk factors for the development of asthma. [ABSTRACT FROM AUTHOR]

Background . Acute responsiveness to inhaled bronchodilators is often used to differentiate between bronchial asthma and chronic obstructive pulmonary disease (COPD). The response can be expressed in terms of a change in FEV 1 and FVC in several ways—as absolute change, change as percent of baseline value, or as percent of predicted value with different thresholds for a positive test. A comprehensive evaluation of the diagnostic value of these different methods of expressing the acute bronchodilator response has not been carried out. Methodology . Response to inhaled salbutamol was measured by spirometry in 200 asthmatics and 154 patients with COPD. The sensitivity, specificity, and positive and negative predictive values of different methods of expressing responsiveness were calculated. Receiver operative characteristic curves were obtained. Results . None of the expressions of response gave a clear-cut separation between the two diseases. A ?FEV 1 = 0.2 L gave the most satisfactory combination of sensitivity (73%) and specificity (80%) and the highest positive (82%) and negative predictive values (69%) for diagnosing asthma. These values were superior to those obtained for the ERS or the ATS criteria for reversibility (?FEV 1 %predicted = 9% and ?FEV 1 of = than 12% and 0.2 L over the baseline, respectively), which had almost similar diagnostic characteristics. This was confirmed by the area under curve of the ROC plots. Expressions of response in terms of changes in FVC were unsatisfactory in separating the two diseases. Conclusions . It was concluded that the test of acute bronchodilator responsiveness has limited diagnostic value in separating asthma and COPD. [ABSTRACT FROM AUTHOR]