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The potential of chronic or acute irritant gas exposures to cause asthma or a variant condition, reactive airways dysfunction syndrome (RADS) was investigated by observing asthma incidence in a large working population, using person-years at risk (P-YR) to compute relative rates (RR). Health data came from employee examinations at 62 pulp and paper plants. The 39122 workers who denied asthma beginning before the observation period included: 19326 denying irritant exposures, with no gassing exposures; 19349 with self-reported irritant exposures, and no gassing; and 447 with documented gassings. Asthma was defined as self-reported asthma beginning after the start of observation. P-YR accrued from September 29, 1986, for the nonexposed and exposed workers, and from date of first gassing for gassed workers, and ended with disease onset in any who developed asthma. RR of asthma with 95% confidence intervals (CI95) were calculated for the exposed and gassed groups, relative to the nonexposed. Exposed (nongassed) workers had an elevated asthma rate, RR=1.48, CI95=1.17-1.86, after adjustment for effects of gender and number of examinations. The rate in gassed workers was not significantly elevated: RR=1.95, CI95=0.75-5.08. Of the five asthma cases occurring after gassings, none conformed to diagnostic criteria for RADS. Chronic exposures were associated with increased rate of asthma onset, which must be interpreted with caution because self-reported data defined both exposure category and disease. Documented gassings were not associated with significantly increased rate, and none of 447 gassed persons developed RADS.

Objective: There are many settings in which a spacer device is not available for the administration of bronchodilator. Therefore, we tested whether a paper disposable cup is as effective as a commercially produced spacer to administer bronchodilator., Methodology: Randomised controlled trial. 50 subjects aged 16-50 years who had wheeze and a greater than 10% decrease in FEV1 after histamine inhalation test (HIT). Subjects were randomised to either the 150 ml paper disposable cup group (CUP) or the commercially produced spacer group (SPACER). Twenty minutes after 400 microg salbutamol was administered FEV1 was measured. The recovery index measured post-bronchodilator FEV1 as a percentage of baseline FEV1. Also, analysis of covariance tested whether recovery of FEV1 was related to the magnitude of the fall following the HIT., Results: There were no statistically significant differences between CUP and SPACER groups in any characteristics. There was no difference for the recovery index (t48=1.14, P=0.26). Regression analyses showed that the relation between the magnitude of the fall in FEV1 during the HIT and the percent recovery was not different between the CUP and SPACER groups (t=-1.2, P<0.23)., Conclusions: A paper disposable cup was effective for the reversal of mild to moderate bronchoconstriction. Therefore, a paper disposable cup can be used for the first-aid management of asthma when there is concern about cross-infection and a commercially produced spacer is not available.

Summary: Aim: To adapt the Asthma Quality of Life Questionnaire (AQLQ(S)), the Asthma Control Questionnaire (ACQ) and the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ(S)) for a personal digital assistant (Palm TX) and to examine the validity of the electronic versions by comparing them with the original paper versions. Methods: 84 adults with asthma and 32 with rhinitis were randomised to complete either the paper or the electronic version first. After 2h, they completed the other version. Results: 68 asthma and 27 rhinitis patients provided analysable data. For the AQLQ(S) and RQLQ(S) differences between paper and electronic were significant. Concordance between paper and electronic, evaluated using an intraclass correlation coefficient were: AQLQ=0.92, ACQ=0.90 and RQLQ=0.85. Concordance for the individual domains of the AQLQ and RQLQ ranged from 0.52 to 0.94. These levels of concordance did not reach the a priori defined requirement for validity. Conclusions: The significant bias between paper and electronic versions and only modest concordance provides evidence that patients may respond differently to questionnaires in different formats and show that different formats must not be used interchangeably. [Copyright &y& Elsevier]

Background: Inhalation flow profiles may affect particle release from dry powder inhalers (DPIs). Currently available measures include a limited number of laboratory-measured parameters such as peak inhalation flow (PIF) and inhaled volume (inhV). We aimed to investigate whether parameters obtained under such conditions are valid in real-world settings and determine the effective inhalation profile., Method: We included seven asthmatics without recent deterioration and regularly inhaling Turbuhaler® or Diskus®. Daily inhalation profiles and particle release from either DPI were measured at home using a newly designed handy analyzer (real-life inhalation events recorder [RLEFR]), for ≥2 weeks. Inhalation pressure drop and signals of particle release during each inhalation were recorded., Results: All patients inhaled daily with similar patient-specific profiles. The mean PIF and inhV were 91.9-31.6 L/min and 0.84-2.05 L, respectively. PIFs were smaller than those obtained in previous laboratory studies, and only one patient exceeded inhV of 2.0 L. The mean flow acceleration and particle emission were 39-571 L/min/s and 0.37-1.54 s, respectively. Particle release was sporadic in one Turbuhaler® user whose PIF was 31.6 L/min, appearing at 1.55 s of inhalation. Particle release from Turbuhaler® appeared to be PIF-dependent, but that from Diskus® was not., Conclusion: Inhalation flow profile measured at home is highly reproducible, but tends to be weaker and shorter than that measured in the laboratory. The results confirm that rapid inhalations from the start are required when using a DPI. RLEFR is a promising device for patient education and clinical studies., Trial Registration Number: UMIN000045193., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: The actual burden of COPD and asthma may be much higher than appreciated, since a large proportion of individuals are not diagnosed. Our study objective was to compare health care utilization, burden of symptoms and quality of life in subjects with self-reported respiratory symptoms who were subsequently found to have undiagnosed airflow obstruction compared to those having no airflow obstruction., Methods: This cross-sectional case-finding study used data from the Undiagnosed COPD and Asthma Population (UCAP) study. Adult subjects with respiratory symptoms who had no history of diagnosed lung disease were recruited in a two-step case-finding process using random digit-dialling of land lines and cell phones located within a 90-min radius of 16 Canadian study sites. Participants were assessed for COPD, asthma or no airflow obstruction using pre- and post-bronchodilator spirometry based on American Thoracic Society diagnostic criteria., Results: 1660 participants were recruited, of these 1615 had adequate spirometry and 331 (20.5%) subjects met spirometry criteria for undiagnosed asthma or COPD. Subjects with undiagnosed asthma or COPD had increased respiratory symptoms as assessed by the COPD Assessment Test (CAT), and higher St. George's Respiratory Questionnaire (SGRQ) scores indicating worse health-related quality of life, compared to subjects with no airflow obstruction. No between-group differences were found in health care utilization or work or school absenteeism., Conclusion: Undiagnosed asthma and COPD are common in Canadian adults experiencing breathing problems and are associated with a greater burden of symptoms and poorer health-related quality of life. These results suggest that patients may benefit from early identification and treatment of undiagnosed asthma and COPD., Competing Interests: Declaration of competing interest All authors in this paper declare that they have no conflict of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Several studies have investigated the physiological effect of OCS in stable asthma, however these have included heterogeneous populations and outcomes. This paper is the first to combine their results., Methods: We searched Medline, Embase and Web of Science databases for studies reporting the impact of OCS on FEV 1 , FVC, blood eosinophils, fractional exhaled nitric oxide (FeNO), Asthma Control Questionnaire (ACQ) score or Asthma Quality Of Life Questionnaire (AQLQ) score in stable asthma. We extracted data on the correlates of OCS response., Results: 61 studies, comprising 1608 patients, were included. FEV 1 was improved by 9% (95% CI: 7, 11). There were stronger increases in FEV 1 among those with a mean baseline FEV 1 <60% predicted (19%, 95% CI: 13, 24). Despite these improvements, substantial residual impairment remained after treatment. Blood eosinophils were reduced by 76% (95% CI: 63, 88) with larger decreases in studies of corticosteroid-naïve patients (93%, 95% CI: 73,100). Sputum eosinophils were reduced by 89% (95% CI: 79, 98) while FeNO was decreased by 35% (95% CI: 28, 41). ACQ scores were reduced by 20% (95% CI: 11, 29). Patients with higher baseline lung function impairment, sputum eosinophils, blood eosinophils and FeNO had improved OCS response., Interpretation: OCS consistently improves lung function, reduces markers of type-2 inflammation, and alleviates asthma symptoms. However, substantial residual impairment remained following treatment and mean improvements were below the minimally important clinically difference. Patients with increased markers of type-2 inflammation are more responsive to treatment, suggesting these should be used to better target OCS use., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: It is essential to recognize and treat findings that can simulate or worsen symptoms to improve asthma control and thereby to reduce costs. Guidelines highlight a paranasal (PS) and chest computed tomography (CT) scan as a tool for disease evaluation and, although they suggest its indication in patients whom presentation is atypical, there are not well-defined criteria., Objectives: To describe the most common findings in the PS and chest CT in severe asthma patients and to analyse the characteristics of asthmatics with the finding of nasal polyps or bronchiectasis., Methods: We retrospectively reviewed the medical records of 161 adults with confirmed severe asthma who had undergone to PS and/or chest CT. Clinical data from their electronic health record and the findings from a PS and/or chest CT within the last five years were collected., Results: In the PS CT, 70.5% of patients presented mucous thickening and 46.7% presented nasal polyps. Both findings were associated with male gender and level of blood eosinophils. In chest CT, 28% of individuals showed atelectasis, 16.5% air trapping, 17.7% affectation of the small airway, 11.6% pulmonary infiltrates and 10.4% emphysema. Bronchiectasis were identified in 60.4% of subjects, who were older and had poorer lung function., Conclusion: Paranasal and thoracic computed tomography are important tools in the treatment of severe asthma because they allow us to detect highly prevalent findings in this disease that can lead to poorer control of it., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Asthma is one of the most common respiratory disorders, characterized by fully or largely reversible airflow limitation. Asthma symptoms can be triggered or magnified during exertion, while physical activity limitation is often present among asthmatic patients. Cardiopulmonary exercise testing (CPET) is a dynamic, non-invasive technique which provides a thorough assessment of exercise physiology, involving the integrative assessment of cardiopulmonary, neuromuscular and metabolic responses during exercise. This review summarizes current evidence regarding the utility of CPET in the diagnostic work-up, functional evaluation and therapeutic intervention among patients with asthma, highlighting its potential role for thorough patient assessment and physician clinical desicion-making., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: To describe trends of hospital admissions due to asthma from 2008 to 2015 and to evaluate their relationship with trends of inhaled corticosteroids (ICS) provision by the government in Brazil., Methods: We used Brazilian Government data to calculate hospital admission rates due to asthma, number of physicians, number of hospital beds, number of subjects that received ICS per 100,000 inhabitants in Brazil and in each of its municipalities for each year of the study. We performed Poisson Multilevel Regression Analyses to evaluate the relationship between the trends of hospital admission rates due to asthma with the trends of the number of subjects that had been receiving ICS during the study period. The analyses were adjusted for the number of physicians and hospital beds., Findings: The number of patients who received ICS/100,000 inhabitants increased from 2008 to 2015 (943.9-1988.5). Hospital admissions/100,000 inhabitants decreased in patients aged 5-14 years (148.3-110.9) and in patients aged 15-39 years (59.9-32.3); the reduction was greater in municipalities in which ICS provision increased. The number of physicians/100,000 inhabitants increased and the number of hospital beds/100,000 inhabitants decreased in the study period. The increase in the number of physicians and in the number of subjects that received ICS were associated with reduction in hospital admissions., Conclusion: We found that provision of ICS by the Brazilian Government was associated with a decrease of hospital admissions for asthma in the municipalities and country levels from 2008 to 2015., Competing Interests: Declaration of competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: The clinical and laboratory features of patients enrolled in the Severe Asthma Network in Italy (SANI) registry, a web-based observatory collecting demographic, clinical, functional and inflammatory data of patients with severe asthma were evaluated, with a special emphasis to chronic rhinosinusitis with nasal polyposis (CRSwNP)., Methods: For each eligible patients the following information has been collected: demographic data, clinical features, asthma control in the previous month according to the GINA (Global INitiative for Asthma) Guidelines and standardized questionnaires, concomitant regular and on demand treatments and inflammatory markers., Results: 695 patients with severe asthma enrolled in 66 SANI centers were analyzed. The prevalence of chronic rhinosinusitis with nasal polyposis was 40.6%. Atopic dermatitis and bronchiectasis was significantly more frequent in patients with CRSwNP than in subjects without nasal polyposis; similarly, FeNO values are significantly higher in subject with CRSwNP than in patients without nasal polyposis. Finally, patients with CRSwNP had a significantly higher number of asthma exacerbations per year, more days on oral corticosteroids and were more likely to be OCS long term users., Conclusion: OCS sparing is needed in patients with severe asthma, mainly in subjects with CRSwNP, adopting adequate strategies such as a better adherence to the treatment with inhaled therapy according to the GINA recommendations, the use of biologic agents and a multidisciplinary approach of the patient., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Asthma is a common chronic disease in childhood, resulting in high costs for health care systems and society. As of June 2011, the Brazilian Unified Health System (SUS) provides free asthma medications for the population. This study evaluated the impact of this program on asthma admissions in the population aged 1-19 years. In addition, a cost-benefit analysis compared data before and after the introduction of the program., Methods: This descriptive study was based on information from SUS Information Technology Department (DATASUS). Admission rates and costs of patients aged 1-19 years with diagnosed asthma were compared before (2008-2010) and after (2012-2017) the provision of free inhaled corticosteroid., Results: The asthma admission rate reduced by 28.4% when comparing the two periods (OR 0.71; 95% CI 0.64-0.79). Children aged 1-4 years had a 27.3% reduction in asthma admissions (OR 0.72; 95% CI 0.63-0.82), while those aged 15-19 years had a 39.65% decrease (OR 0.59; 95% CI 0.37-0.95). Asthma admission costs decreased when comparing the two periods (OR 0.68; 95% CI 0.62-0.74). After the introduction of the program, mean cost savings reached US $27,865,905.08 in children aged 1-4 years and US $21,350,660.63 in those aged 5-19 years., Conclusion: The economic burden of pediatric asthma on Brazil's public health care system is significant. From 2012 to 2015, free provision of inhaled corticosteroid was cost-effective in all age groups. In 2017, no cost-benefit effect was observed in this population, but asthma admission rate decreased., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Competing Interests: Declaration of competing interest The authors declare that they have no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Background: Severe asthma affects less than 5% of asthmatics, but is associated with high costs and increased mortality. The aim of this study was to assess age- and sex-dependent differences in this patient group., Methods: Retrospective analysis of 1317 children and adults with severe asthma who are included in the German Asthma Net registry., Results: There were more adults than children in the registry and patients' mean age was 52. Apart from children <18 years, there were more women (57%) than men. The age of first diagnosis ranged from 0 to 76 years. 38% of patients had a positive bronchial reversibility after short acting bronchodilators. Quality of life, FEV1 and MEF 25 decreased with older age whereas treatment with oral steroids and monoclonal antibodies increased. An anti-eosinophil treatment was most frequently used in patients aged around 57 years, while an anti-IgE treatment was used in all age-groups including children. There were sex-dependent differences with lower values in men for FEV1, FVC, MEF 25 and DLCO. Yet, women were more frequently unable to work than men due to the disease., Conclusion: In patients with severe asthma, clinical characteristics, but also treatments differed between age groups and between the sexes, reflecting different phenotypes of the disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Rationale: Although the methacholine challenge test is useful in the diagnosis of asthma, it is time-consuming in children. While protocols that quadruple methacholine concentrations are widely used in adults to shorten testing time, this has not been evaluated in children. Studies have not identified predictors associated with the safe use of a quadrupled concentration protocol., Objectives: To identify clinical predictors associated with the preclusion of a quadrupled concentration protocol in children., Methods: We included subjects <18 years who performed a methacholine challenge tests between April 2016 to February 2017 (derivation cohort) and March 2017 to September 2017 (validation cohort). We determined the eligibility of a subject to omit the 0.5 mg/ml and 2.0 mg/ml concentrations based on their PC20 and identified baseline characteristics that are associated with the preclusion of the quadrupled protocol using bivariate analysis. The derived algorithm was applied to the validation cohort., Results: We included 399 and 195 patients in the derivation and validation cohorts, respectively. A baseline FEV 1 ≤90% predicted, FEV 1 /FVC ≤0.8, FEF 25-75 ≤70% predicted, and a decrease in FEV 1 ≥10% with the previous concentration significantly precluded the omission of the 0.5 mg/ml concentration. A baseline FEF 25-75 ≤70% predicted and a drop in FEV 1 ≥10% with the previous concentration significantly precluded the omission of the 2.0 mg/ml concentration. Applying these 4 criteria to the validation cohort resulted in an overall sensitivity and specificity of 74.0% and 84.6%, respectively., Conclusions: We identified objective pulmonary function measures that may personalize and shorten the methacholine challenge protocol in children by quadrupling concentrations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019. Published by Elsevier Ltd.)

Background: Non-adherence to asthma treatment is a contributing factor for poorly controlled asthma., Aim: The aim of this systematic review is to explore patients' perceptions of their inhaled asthma treatment, and how these relate to adherence, using both qualitative and quantitative data., Methods: Pre-determined search terms and inclusion criteria were used to search electronic databases (The Cochrane Library, MEDLINE, EMBASE and PsycINFO). Two researchers screened titles and abstracts using the Rayyan web app and data were extracted in relation to psychological components (beliefs about, and attitudes towards, medicines) and adherence., Results: Of 1638 papers, 36 met the inclusion criteria. Key themes were: Perceived need for treatment - all 12 studies using the BMQ to measure patients' perceived need for treatment found that patients' beliefs about their necessity for treatment were associated with adherence-; Concerns about treatment - immediate and long-term side effects (58%), worries about safety (19%), and potential addiction to asthma medication (31%)-; and Perceived social stigma - 22% of studies reported that embarrassment contributed to poor adherence., Conclusions: Acknowledging and addressing patient treatment beliefs and perceptual barriers to adherence is integral to designing adherence interventions for asthma patients. Further research is needed to better our understanding of the relationship between treatment perceptions and adherence., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The area of asthma medicine has produced a large volume of important clinical and scientific papers that can be found in those most influential journals. The purpose of our study was to identify the 100 most cited papers in asthma research and to analyze their characteristics., Methods: We used the Institute for Scientific Information Web of Knowledge Database to identify the most frequently cited articles published from 1960 to December 2017. Original articles and reviews were included in the study. The 100 top-cited articles were then analyzed with regard to number of citations, publication year, journals, institution, research type and field, authors and countries of authors of publications., Results: The 100 top-cited articles in asthma were published between 1960 and 2011 with a median of 933 citations per article (range, 701-2947). The number of citations per article was greatest for articles published in the 1990s. The United States of America contributed most of the classic articles, followed by England. The leading institutions were Imperial College London, McMaster University, Erasmus University Rotterdam. The 100 top-cited articles were published in twenty-five journals, led by The New England Journal of Medicine (21 articles), followed by American Journal of Respiratory and Critical Care Medicine (19 articles), Lancet (11 articles), respectively. Among the 100 classics, 50% articles were clinical research articles., Conclusions: Our study provides a historical perspective on the progress of research on asthma. Studies conducted in well-developed European countries and North America, published in high-impact journals had the highest citations., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Asthma and allergic diseases can start in childhood and persist throughout life, but could also be manifested later, at any time for still misunderstood reasons. They are major chronic multifactorial respiratory diseases, for which prevention, early diagnosis and treatment is recognized as a priority for the Europe's public health policy and the United Nations. Given that allergy triggers (including infections, rapid urbanization leading to loss in biodiversity, pollution and climate changes) are not expected to change in a foreseeable future, it is imperative that steps are taken to develop, strengthen and optimize preventive and treatment strategies. Currently there are good treatments for asthma, several risk factors are known (e.g., allergies, rhinitis, tobacco smoke) and tools to control the disease have been developed. However, we are still uncertain how to prevent patients from developing asthma and allergic diseases. In this paper, we list the positive and negative experiences in this field as well as analyze the missing links in the process. This critical analysis will be the basis of setting-up an effective program for prevention and making, a process labeled as "implementation gaps"., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objectives: The purpose of this paper is to examine whether high school students in Ontario with asthma smoke cigarettes, waterpipes, marijuana or e-cigarettes more or less than those without asthma., Methods: The 2013 Ontario Student Drug Use and Health Survey provides self-report data on tobacco cigarettes, waterpipes, marijuana and e-cigarette smoking and asthma rates from 109 high schools in Ontario, Canada. Individual and social characteristics were also collected. Multiple binary logistic regression models measures the association with the various types of smoking in relation to asthma., Results: Adolescents with asthma have higher odds of smoking e-cigarettes or smoking any type including either cigarettes, waterpipes, marijuana or e-cigarettes. Respondents of lower socio-economic status had a higher odds of smoking marijuana or any type. Boys were more likely to smoke waterpipes, e-cigarettes or any type, while students in higher grades had a higher odds of smoking cigarettes, waterpipes, marijuana or any type., Conclusions: Results from this study suggest that adolescents with asthma have a higher odds of smoking e-cigarettes than those without asthma, but no relationship was found for cigarettes, waterpipes or marijuana. Findings present some new challenges as technology changes how adolescents can smoke. Public health campaigns should target adolescents, especially those with asthma, to raise their awareness of the risks of all types of smoking including e-cigarettes., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Asthma may be associated with polycystic ovary syndrome (PCOS), and possibly patients with PCOS have a more severe type of asthma. The purpose of this systematic literature review is to summarize evidence of a coexistense of PCOS and asthma using the available literature. The search was completed on 01.01.2016. English language articles were retrieved using the search terms 'Asthma' AND 'PCOS', 'Asthma' AND 'systemic inflammation', 'Asthma' AND 'metabolic syndrome', 'asthma' AND 'gynaecology', 'PCOS' AND 'systemic inflammation', 'PCOS' AND 'metabolic syndrome', 'PCOS' AND 'allergy'. Five papers meeting prespecified search criteria were found of which two were registry studies of relevance. The current literature supports a coexistense of PCOS and asthma and gives us an indication of the causes for the possible link between PCOS and asthma. Further research in the area must be conducted to determine the exact nature and magnitude of the association., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background and Aim: Epidemiological data has established increasing adiposity as a risk factor for incident asthma. However, the mechanisms underlying the association between obesity and asthma are incompletely understood. In the present paper, we review current knowledge of possible mechanisms mediating the observed association between obesity and asthma., Methods: Systematic literature review., Results: Obesity and asthma share some etiological factors, such as a common genetic predisposition and effects of in utero conditions, and may also have common predisposing factors such as physical activity and diet. Obesity results in important changes in the mechanical properties of the respiratory system which could explain the occurrence of asthma. However, there are also plausible biological mechanisms whereby obesity could be expected to either cause or worsen asthma. These include co-morbidities such as gastro-oesophageal reflux, complications from sleep-disordered breathing, breathing at low lung volumes, chronic systemic inflammation, and endocrine factors, including adipokines and reproductive hormones. Obesity related asthma is in general not associated with eosinophilic airway inflammation, and adipokines are likely to play important roles in the inflammatory pathogenesis of asthma in obese individuals., Conclusion: The association between obesity and asthma is not straightforward, and further knowledge is clearly needed, as understanding the underlying mechanisms may lead to new therapeutic options for this high-risk part of the asthma population., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: The Mini Asthma Quality of Life Questionnaire (MiniAQLQ) is a validated disease-specific quality of life (QOL) paper (p) questionnaire. Electronic (e) versions enable inclusion of asthma QOL in electronic medical records and research databases., Purpose: To validate an e-version of the MiniAQLQ, compare time required for completion of e- and p-versions, and determine which version participants prefer., Methods: Adults with stable asthma were randomized to complete either the e- or p-MiniAQLQ, followed by a 2-h rest period before completing the other version. Agreement between versions was measured using the intraclass correlation coefficient (ICC) and Bland-Altman analysis., Results: Two participants with incomplete p-MiniAQLQ responses were excluded. Forty participants (85% female; age 47.7 +/- 14.9 years; asthma duration 22.6 +/- 16.1 years; FEV(1) 87.1 +/- 21.6% predicted) with both AQLQ scores <6.0 completed the study. Agreement between e- and p-versions for the overall score was acceptable (ICC=0.95) with no bias (difference (Delta) p-e=0.1; P=0.21). ICCs for the symptom, activity limitation, emotional function and environmental stimuli domains were 0.94, 0.89, 0.90, and 0.91 respectively. A small but significant bias (Delta=0.3; P=0.004) was noted in the activity limitation domain. Completion time was significantly longer for the e-version (3.8 +/- 1.9min versus 2.7 +/- 1.1min; P<0.0001). The majority of patients (57.5%) preferred the e-MiniAQLQ; 35% had no preference., Conclusion: This e-version of the MiniAQLQ is valid and was preferred by most participants despite taking slightly longer to complete. Generalizabilty may be limited in younger (12-17) and older (>65) adults.

Appeared at the beginning of the 20th century, allergen-specific immunotherapy (SIT) has long been used in allergic rhinitis and asthma without any knowledge of its mechanisms of action or any tangible proof of its efficacy. However, from the beginning of the era of evidence-based medicine, a number of placebo-controlled studies have been published and reached a sufficient number to assess the cellular events induced by SIT and allow meta-analysis to provide guidelines based on proofs. Controlled studies and meta-analysis concerned not only subcutaneous immunotherapy but also the sublingual route, demonstrating an effect of SIT on symptoms and medication use. Most recently sublingual tablets were proposed in allergic rhinitis. This paper reviews the mechanisms of SIT, the evidence of efficacy of SIT from the injective to the sublingual route and reminds the current guidelines.

Background: EQ-5D is a generic preference-based measure of health that can help to understand the impact of asthma and chronic obstructive pulmonary disease (COPD). The purpose of this paper was to synthesize literature on the validity and reliability of EQ-5D use in studies of asthma and COPD, and estimate EQ-5D utility scores associated with stage of disease., Methods: A structured search was conducted in EMBASE and MEDLINE (1988-2007) using keywords relevant to respiratory disease and EQ-5D. Original research studies in asthma or COPD that reported EQ-5D results and/or psychometric properties were included., Results: Studies that reported psychometric properties supported the construct validity, test-retest reliability, and responsiveness of EQ-5D in asthma (seven studies) and COPD (nine studies), although some evidence of ceiling effects were observed in asthma studies. In asthma studies that reported summary scores (n=11), EQ-5D index-based scores ranged from 0.42 (SD 0.30) to 0.93 (SD not reported). In COPD studies (n=8), scores ranged from 0.52 (SD 0.16) to 0.84 (SD 0.15). While few asthma studies reported scores by severity level, sufficient studies in COPD were available to calculate pooled mean utility scores according to GOLD stage: stage I=0.74 (0.62-0.87), stage II=0.74 (0.66-0.83), stage III=0.69 (0.60-0.78) and stage IV=0.61 (0.44-0.77) (most severe)., Conclusions: Evidence generally supported the validity and reliability of EQ-5D in asthma and COPD. Utility scores associated with COPD stage may be useful for modeling health outcomes in economic evaluations of treatments for COPD.

Corticosteroids are effective anti-inflammatory medications that are recommended for the control of persistent asthma. Little, however, is known about their influence on the perception of dyspnea, which, in turn, is important to the successful self-management of asthma. This paper provides a synopsis of available studies examining the impact of corticosteroids on the sensitivity to perceive dyspnea and presents possible mechanisms underlying this relationship. The results of these investigations are conflicting with some studies showing improved perception and other studies showing worsened perception of dyspnea after corticosteroid treatment. Thus, firm conclusions cannot be derived from the currently available data. Implications for future research, which is required to increase our understanding of potential influences of corticosteroids on the perception of dyspnea, are provided.

Introduction: Eosinophil cationic protein (ECP) has been widely investigated as a potential biomarker of airway inflammation., Method: A systematic review was performed using Medline with key terms eosinophil cationic protein and asthma, limiting the search to titles or abstracts. Out of 688 potential papers found, abstracts were reviewed based on the following criteria: (1) ECP was used as a biological marker, (2) asthma was the index disease studied, (3) it was a controlled clinical study and (4) ECP was assessed as a diagnostic, assessment or management tool. One hundred and sixty-nine articles satisfied the selection criteria and their full-text versions were reviewed. Only 53 papers were found to provide clinically useful information., Results: ECP has been measured in serum, plasma, sputum, saliva and broncho-alveolar lavage fluids but serum and sputum are the most established. Levels of ECP in normal and asthmatic subjects in various body fluids were identified. ECP correlates well with airway inflammation but not airway hyper-responsiveness. It is raised in other atopic diseases and hence is not diagnostic for asthma. However, it has been shown to be useful in assessing asthma severity, compliance with anti-inflammatory asthma therapy and as a guide to tailing down inhaled corticosteroid therapy. Although there is some evidence that ECP levels are affected by age, smoking, circadian rhythm and seasonal variation, only smoking appears to be of clinical significance., Discussion: Despite its limitations, ECP remains potentially useful in asthma management. Future research on ECP should focus on using serial measurements and combining it with other markers of asthma which may increase its clinical usefulness.

In the choice of, or switch between, various inhaled corticosteroids (ICS) it is important to know equipotent doses for clinical treatment effects of the alternatives. Various ICS do have different inherent potency. Further, the ICS are delivered from inhalers that may differ markedly in output characteristics and drug delivery to intrapulmonary airways. Therefore, clinical efficacy comparisons must include drug-inhaler comparisons. We estimated the therapeutic potency ratio of the Flixotide Diskus (fluticasone propionate, FP) and the Pulmicort Turbuhaler (budesonide, BUD) in steroid-naive asthma patients, using a dose-reduction technique (FP 500-0 mcg/day, BUD 800-0 mcg/day). The dose defining end point was loss of asthma control in this paper denoted as exacerbation. In total, 282 patients with proven asthma were enrolled in the study, and 103 in the FP group and 98 in the BUD group completed the study per protocol. In total, 80 patients in the FP-group and 79 in the BUD-group experienced a dose defining exacerbation. The exacerbation frequency increased in a dose-dependent way as the dose was titrated down. From these data the potency difference between the present drug inhaler combinations, Flixotide Diskus and Pulmicort Turbuhaler, was calculated to be between 1.50:1 (95% CI 1.10:1-2.05:1) and 1.75:1 (CI 1.26:1-2.43:1) depending on if patients with insufficient steroid-response were excluded from the calculations or not. In these steroid-naïve patients, the potency difference was evident only at low daily doses, below 200 mcg.

Asthma is a chronic disorder, characterized by airway hyperresponsiveness (AHR), airway inflammation and airway remodelling. Evidence has been provided for a relationship between pathophysiology, airway inflammation and remodelling. Moreover, these asthma features have been shown to respond to anti-inflammatory therapy. According to current guidelines, monitoring of asthma is predominantly based on symptoms and lung function data. However, these parameters appeared as poor indices for asthma control. Alternatively, asthma control relates well to exacerbations and (anamnestic) surrogate biomarkers of airway inflammation. Hence, appropriate treatment of asthma should primarily target the airway inflammation. According to current guidelines for asthma management, anti-inflammatory therapy with inhaled corticosteroids (ICS) is the cornerstone in the treatment of persistent asthma. To further optimize asthma control, add-on therapy with long-acting beta2-agonists (LABA) or leukotriene receptor antagonists (LTRA) should be combined with low to high doses of ICS. While the first combination focuses on optimal control of symptoms and lung function, the second provides a more complete suppression of the airway inflammation. In this paper we discuss treatment of asthma according to current guidelines versus new insights, addressing practical issues.

Adherence to asthma medication regimens by asthma patients is often poor and contributes to the continued and substantial burden of asthma in the community. There is evidence of increased rates of behavioural problems, anxiety and depression in people with moderate-to-severe asthma and these factors may interfere with adherence and contribute to poor asthma control. An alternative explanation is that the relationship between feelings of anxiety and depression, and adherence to the treatment regimen may be more accurately predicted from the coping styles used, rather than the experience of asthma itself. The objective of this paper was to review evidence for associations between coping strategies used by asthma patients, asthma management and health outcomes. The Medline and PsychInfo databases were searched for articles containing the terms "asthma" and "coping". Patients with asthma tended to use different strategies for coping with stress and illness compared to healthy participants and individuals with other chronic illnesses. Emotion-focussed coping strategies such as denial were commonly used by patients with poor medication adherence, those who attended emergency departments for asthma, were admitted to hospital for asthma, or suffered near-fatal asthma attacks. Interventions to improve coping strategies have been effective in reducing symptoms and psychological distress. The availability of coping resources to patients and/or their caregivers and the coping strategies that are used are likely to mediate the influence of psychosocial factors on the management of asthma. Further studies exploring the ways in which individuals cope with asthma will improve our understanding of the mechanisms linking psychological and social status to asthma morbidity and mortality.

Formal economic evaluation is playing an increasingly important role in health-care decision-making. This is shown by the requirement to present economic data to support applications for public reimbursement for new pharmaceuticals in Australia and the provinces of Canada, and by the appraisal process initiated by the National Institute for Clinical Excellence in the U.K. This growing role of economic analysis applies as much to the field of asthma as anywhere. This paper provides a detailed review of applied economic studies in asthma. The review is used to explore a range of methodological issues in the field including the choice of perspective and maximand, whether to use disease-specific or generic measures of outcome and whether decision-makers should receive disaggregated cost and consequence data or results that focus on an incremental cost-effectiveness ratio. It is concluded that, given the heterogeneity in decision-makers' objectives and constraints, economic studies should be planned and executed in such a way as to maximize flexibility in how results are presented.

We have proposed a clinical treatment guideline for the management of acute, severe asthma and chronic obstructive pulmonarydisease (COPD) using the principles of evidence-based medicine. The content is based upon practical clinical issues in need of consensus. A previous study has shown that this particular area is in serious need of quality control. Based on a strict 2 h time schedule with a unified treatment plan for both asthma and COPD, it is possible to secure for the patients a well-documented medical therapy promoting decision-making and clarification of the patient within this time limit. A summary of the statements is presented in a one-page, user-friendly format in order to cope with the clinician's need of having access to published evidence quickly and easily. A website (www.phanareth.dk or a website provided by Respiratory Medicine) has been established providing regular updates. A strategy for the implementation and the evaluation process has been planned after the publication of this paper. We believe this approach to be an important step towards an increase in the quality of guidelines and also a tool to make "guideline writers" aware of the responsibility of making their recommendations work.

Asthma is now widely recognized as a chronic inflammatory condition of the airways that requires early pharmacological treatment and long-term management. Anti-inflammatory agents, particularly inhaled corticosteroids, are currently the most effective long-term preventative medication. Moreover, early intervention with inhaled corticosteroids plays an important role in airway remodelling. Despite significant advances in the understanding of asthma and its pharmacological management, the prevalence of asthma in children, teenagers and young adults is on the increase. For patients whose asthma is not fully controlled with daily inhaled corticosteroid therapy, national guidelines advocate the addition of long-acting inhaled beta2-agonist therapy, rather than an increase in dose of inhaled corticosteroids, for the treatment of persistent childhood asthma. However, adherence to treatment with asthma medication declines as the regimen becomes more complicated. Adherence to therapy and therapy convenience are key to the successful pharmacological management of asthma, particularly in children. The administration of prescribed medication via a single inhaler offers a convenient treatment regimen that has the potential to improve adherence to treatment. This paper presents data to show that the combined administration of budesonide and formoterol via a single inhaler (Symbicort Turbuhaler) is effective and well tolerated in the treatment of asthma in children.

Lung function (FEV1 before and after bronchodilatation) was studied prospectively over five visits in 55 asthmatic children (28 boys) from childhood to adulthood (age 30). At the last follow-up recordings were made at rest, after cold air challenge (CACh), and after bronchodilatation. Results were related to clinical asthma scoring and to sensitization to furred animals, as described in a companion paper. Lung function outcome was shown to be influenced by initial FEV1 (% predicted) and gender, but not by initial asthma severity or sensitization. FEV1 (% predicted) was higher in females than in males over the first two follow-ups, but the reverse was found over the subsequent visits. It deteriorated from childhood to adulthood in the females but improved in the males. In adulthood the females (for height 170 cm) had a steeper normalized annual fall in post-bronchodilator FEV1 than the males (55 +/- 38 vs. 25 +/- 36 ml; P = 0.006). The degree of bronchial hyperresponsiveness was associated significantly with asthma severity and the extent of sensitization to furred animals, but not with gender. The results indicate a better lung function outcome for asthmatic boys than for girls, confirming trends seen in clinical asthma severity. In adulthood the extent of sensitization to relevant perennial inhaled allergens significantly influences airway responsiveness and asthma severity, but not lung function.

Both albuterol and nedocromil sodium have been recognized to possess certain anti-inflammatory properties. However, there are no data on the impact of these drugs on the pathophysiology of the bronchial extracellular matrix in asthma characterized by enhanced tenascin (Tn) expression, known to occur proportional to the severity of asthma. This paper reports data from a morphometric study on the effects of regular treatment with inhaled albuterol or nedocromil sodium on the extent of bronchial subepithelial deposition of Tn, collagen types III, IV, and VII and mucosal infiltration with macrophages. Thirty-two patients (14 women) with chronic asthma, aged 38.7 years (median) with a median forced expiratory volume in 1 sec (FEV1) of 74.4% predicted, were selected to undergo fibre-optic bronchoscopy with bronchial biopsies before and after 12 weeks of treatment with either inhaled albuterol 0.2 mg or nedocromil sodium 4 mg four times daily according to a double-blind protocol. Cryostat sections of the biopsy specimens were studied by indirect immunostaining techniques using monoclonal antibodies and computer-assisted quantitative image analysis. Albuterol treatment significantly reduced the median thickness of subepithelial Tn expression from 9.7 to 6.3 microns (P = 0.023) and macrophage numbers in the epithelium (P = 0.034), lamina propria (P = 0.039) and entire mucosa (P = 0.033), whereas nedocromil sodium had no effect. Expression of the collagen types was not affected by either treatment. There was no identifiable statistical difference between the two treatments for any of the outcome variables measured. Nevertheless, the results demonstrate that even a short-acting beta 2-agonist may exert anti-inflammatory potential sufficient to interfere with the basic mechanisms of asthma as shown by reduction of subepithelial Tn content and mucosal macrophage count.

Recorded cases of asthma have increased in recent years. It is unclear, however, whether this apparent increase in prevalence is accompanied by an increase in severity of the disorder. One potential measure of asthma severity is the requirement for mechanical ventilation. This paper examines those patients ventilated for severe asthma in a district general hospital over a 17 yr period. Since the methods used to assess asthma attacks and the criteria for instituting mechanical ventilation in this hospital did not alter between 1973 and 1992 (Jones criteria), it was possible to compare directly characteristics of all ventilated patients during the study period. The comparison showed that there was a significant increase between the two study periods in the number of patients who required mechanical ventilation. Moreover, in the more recent period both the subjective speed of onset of the asthma attack and the objective time between admission and ventilation were significantly shorter. However, despite this increase in asthma severity the mortality and morbidity in the more recent study period were lower. Overall the results of this study support the view that, in the population served by our district general hospital, asthma has increased in severity. This increased severity is indicated by an increase in the number of patients requiring mechanical ventilation and in the rapidity with which attacks evolved. However, for patients in whom ventilation was required, improved care has lowered both morbidity and mortality.

Although home nebulizers are widely used to deliver bronchodilator medication to patients with asthma and chronic obstructive pulmonary disease (COPD), the long-term benefits and hazards are unknown. The present authors have previously reported a prospective 12-month study of home nebulizer use involving 49 patients (15 asthma, mean forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) 1.3/2.1 1; 34 COPD, mean FEV1/FVC 0.7/1.8 1). Thirty-two of these patients were treated with long-term domiciliary nebulized bronchodilator treatment, the other 17 patients chose metered dose inhaler (MDI) therapy. The present paper reports the progress of these patients over 5 yr. Five-year survival was similar in both groups (nebulizer users 56%, MDI users 53%). Most deaths were due to respiratory failure (14 deaths) or lung cancer (four deaths). Survival was determined mainly by FEV1 (R = 0.54, P = 0.0001) and age (R = -0.47, P = 0.0007). Laboratory lung function tests (16 nebulizer users) showed that FEV1 and FVC were still higher than pre-nebulizer baseline measurements after 36 months of nebulizer use, but PEFR had fallen by 7%. Twenty-one of 23 surviving nebulizer users completed a questionnaire after 36 months of treatment. All used their nebulizer at least once per day and 20 of 21 patients reported that they still obtained full benefit from each nebulized treatment. The morning peak flow response to nebulized treatment was the same at baseline and at 36 months (48 1 min-1). All patients remained breathless (mean subjective score 4.8 on seven-point scale) but the subjective response to nebulized treatment was unchanged at 36 months. Tachyphylaxis did not develop among 13 patients who underwent repeated reversibility studies using 200 micrograms of salbutamol at 6, 12 and 36 months. It is concluded that home nebulizer therapy is safe and effective for a small number of carefully selected patients with severe asthma or COPD, who have been evaluated by a rigorous home nebulizer assessment protocol prior to commencing home nebulizer therapy.

The use of inhaled corticosteroids in bronchial asthma has widened, but there is a lack of data on their effect on bone collagen synthesis and degradation. This paper reports the effect of three dose levels (200, 1000 and 2000 micrograms day-1, 3 weeks each) of inhaled beclomethasone on specific characteristics of bone collagen metabolism in seven postmenopausal women with new asthma without any previous corticosteroid therapy. Serum aminoterminal (PINP) propeptide of human type I procollagen was seen, after an initial increase, to decrease significantly (from 42.2 to 35.5 micrograms l-1, P = 0.001) with the higher doses of inhaled beclomethasone, but no statistical change was found in the carboxyterminal propeptide (PICP) or type I collagen crosslinked telopeptide (ICTP). This data shows that type I collagen synthesis may be disturbed when using high-dose inhaled corticosteroids. However, further studies are needed to assess the effects of inhaled beclomethasone on the ability of the osteoblasts to form bone matrix, and on the density of bone during a longer treatment period with inhaled corticosteroids.

Background: This study is part of the European Community Respiratory Health Survey (ECRHS), which uses a common methodology in different areas throughout the world. This paper describes the prevalences of reported asthma, asthma-like symptoms and nasal allergies, their relationships to age group and sex, and the relationships of asthma-like symptoms to current asthma, in the general population aged 20-44 years of three French urban areas., Methods: The study population of 2804 subjects in Grenoble, 3774 in Montpellier and 3152 in Paris (18th district), randomly selected from electoral rolls, answered a postal questionnaire (stage I of ECRHS). The response rates were 77.8%, 68.6% and 74.4%, respectively., Results: The prevalences were approximately 14% for wheezing, 16% for chest tightness and 4.5% for nocturnal shortness of breath in the three areas. Asthma attacks in the last 12 months were reported by 2.7% of subjects in Grenoble, 3.5% of subjects in Montpellier and 4.0% of subjects in Paris (P = 0.02). For nasal allergies, the prevalences were 28.0%, 34.3% and 30.8%, respectively (P < 0.001). Asthma was inversely correlated to age (higher prevalence in the youngest) but was not related to sex. Neither age distribution nor sex ratio explained the differences between areas. Among the asthma-like symptoms, wheezing and nocturnal shortness of breath correlated strongly with asthma, chest tightness correlated moderately and nocturnal coughing correlated poorly., Conclusion: The prevalences observed were higher than expected from previous comparable French studies in young adults. These results are consistent with the hypothesis of a recent increase of asthma and allergies.

Summary: Aging is associated with modifications of the immune system, defined as immunosenescence. This could contribute to a reduced prevalence of allergic disease in the elderly population. In this regard, atopy has rarely been considered in the clinical assessment of the geriatric respiratory patient. This article is a review of the available literature assessing the impact of age on atopy. In the majority of papers, we found a lower prevalence of atopy in the most advanced ages, both in healthy subjects and in individuals affected by allergic respiratory diseases. Unfortunately, no large, longitudinal studies performed in the general population have been conducted to further explore this observation. Although available data seem to favor the decline of allergen sensitization with age, the prevalence of allergic sensitizations in the elderly population with respiratory symptoms is substantial enough to warrant evaluation of the atopic condition. From a clinical perspective, allergic reactions in older adults can have the same or even worse manifestations compared to young people. For this reasons, the evaluation of the atopic condition also in the geriatric patient is recommended. Thus, the role of atopy as it pertains to the diagnosis, therapy (adoption of preventive measure such as removal of environmental allergen or immunotherapy), and prognosis (influence on morbidity and mortality) of chronic respiratory illnesses in the elderly is addressed. [ABSTRACT FROM AUTHOR]

Summary: Background: EQ-5D is a generic preference-based measure of health that can help to understand the impact of asthma and chronic obstructive pulmonary disease (COPD). The purpose of this paper was to synthesize literature on the validity and reliability of EQ-5D use in studies of asthma and COPD, and estimate EQ-5D utility scores associated with stage of disease. Methods: A structured search was conducted in EMBASE and MEDLINE (1988–2007) using keywords relevant to respiratory disease and EQ-5D. Original research studies in asthma or COPD that reported EQ-5D results and/or psychometric properties were included. Results: Studies that reported psychometric properties supported the construct validity, test–retest reliability, and responsiveness of EQ-5D in asthma (seven studies) and COPD (nine studies), although some evidence of ceiling effects were observed in asthma studies. In asthma studies that reported summary scores (n=11), EQ-5D index-based scores ranged from 0.42 (SD 0.30) to 0.93 (SD not reported). In COPD studies (n=8), scores ranged from 0.52 (SD 0.16) to 0.84 (SD 0.15). While few asthma studies reported scores by severity level, sufficient studies in COPD were available to calculate pooled mean utility scores according to GOLD stage: stage I=0.74 (0.62–0.87), stage II=0.74 (0.66–0.83), stage III=0.69 (0.60–0.78) and stage IV=0.61 (0.44–0.77) (most severe). Conclusions: Evidence generally supported the validity and reliability of EQ-5D in asthma and COPD. Utility scores associated with COPD stage may be useful for modeling health outcomes in economic evaluations of treatments for COPD. [Copyright &y& Elsevier]