How to interpret reduced forced expiratory volume in 1 s (FEV1)/vital capacity ratio with normal FEV1.

The aim of the present study was to determine whether the combination of low forced expiratory volume in 1 s (FEV(1))/vital capacity (VC) ratio with normal FEV(1) represents a physiological variant or a sign of early airflow obstruction. We studied 40 subjects presenting with low FEV(1)/VC, but FEV(1) within the range of normality predicted by European Respiratory Society reference equations, and 10 healthy controls. All subjects completed two questionnaires and underwent comprehensive pulmonary function testing, which included methacholine challenge and single-breath nitrogen wash-out. According to the questionnaires, the subjects were assigned to three groups, i.e. rhinitis (n = 8), bronchial asthma (n = 13) and chronic obstructive pulmonary disease (COPD; n = 12). Subjects with negative responses to questionnaires were assigned to an asymptomatic group (n = 7). Airway hyperresponsiveness was found in four subjects of the rhinitis group, all of the asthma group, and 10 of the COPD group; in the last two groups, it was associated with signs of increased airway closure and gas trapping. Bronchodilator response to salbutamol was positive in only a few individuals across groups. In the asymptomatic group, no significant functional changes were observed, possibly suggesting dysanaptic lung growth. In subjects with low FEV(1)/VC and normal FEV(1), questionnaires on respiratory symptoms together with additional pulmonary function tests may help to clarify the nature of this pattern of lung function.

Changes in lung volumes and airway responsiveness following haematopoietic stem cell transplantation.

Changes in lung volume occur following haematopoietic stem cell transplantation (HSCT); airway hyperresponsiveness was occasionally reported, without mechanistic explanation. The present authors studied 17 patients by standard methacholine (MCh) challenge before and then 3 and 12 months after HSCT (n = 16 and n = 13, respectively). Another 6 patients were challenged before and 3 months after HSCT using a modified challenge to investigate the effect of deep inhalations. No patient developed bronchiolitis obliterans or bronchiolitis obliterans organising pneumonia. At 3 months, forced vital capacity (FVC) was significantly reduced by 0.33+/-0.55 L, forced expiratory volume in one second (FEV(1)) by 0.31+/-0.50 L, total lung capacity (TLC) by 0.39+/-0.37 L and single-breath diffusing capacity of the lung for carbon monoxide (D(L,CO)) by 15+/-12%. At 12 months, TLC decreased by 0.43+/-0.36 L and D(L,CO )by 8+/-8%. With standard challenge, no significant changes in FEV(1) response to MCh were observed after HSCT but FVC decreased significantly less after HSCT compared with prior to HSCT, suggesting less air trapping. With modified challenge, deep inhalations reversed the MCh-induced decrease in partial expiratory flow more after HSCT compared with before HSCT and this correlated with TLC decrements. In conclusion, an increase in airway responsiveness is unlikely after haematopoietic stem cell transplantation, at least in patients without pulmonary complications, and mechanisms opposing airway narrowing may blunt the bronchoconstrictor response.

Outcomes for COPD pharmacological trials: from lung function to biomarkers.

The American Thoracic Society/European Respiratory Society jointly created a Task Force on "Outcomes for COPD pharmacological trials: from lung function to biomarkers" to inform the chronic obstructive pulmonary disease research community about the possible use and limitations of current outcomes and markers when evaluating the impact of a pharmacological therapy. Based on their review of the published literature, the following document has been prepared with individual sections that address specific outcomes and markers, and a final section that summarises their recommendations.

Treatment of exercise-induced asthma, respiratory and allergic disorders in sports and the relationship to doping: Part II of the report from the Joint Task Force of European Respiratory Society (ERS) and European Academy of Allergy and Clinical Immunology (EAACI) in cooperation with GA(2)LEN.

AIM: The aims of part II is to review the current recommended treatment of exercise-induced asthma (EIA), respiratory and allergic disorders in sports, to review the evidence on possible improvement of performance in sports by asthma drugs and to make recommendations for their treatment. METHODS: The literature cited with respect to the treatment of exercise induced asthma in athletes (and in asthma patients) is mainly based upon the systematic review given by Larsson et al. (Larsson K, Carlsen KH, Bonini S. Anti-asthmatic drugs: treatment of athletes and exercise-induced bronchoconstriction. In: Carlsen KH, Delgado L, Del Giacco S, editors. Diagnosis, prevention and treatment of exercise-related asthma, respiratory and allergic disorders in sports. Sheffield, UK: European Respiratory Journals Ltd, 2005:73-88) during the work of the Task Force. To assess the evidence of the literature regarding use of beta(2)-agonists related to athletic performance, the Task Force searched Medline for relevant papers up to November 2006 using the present search words: asthma, bronchial responsiveness, exercise-induced bronchoconstriction, athletes, sports, performance and beta(2)-agonists. Evidence level and grades of recommendation were assessed according to Sign criteria. RESULTS: Treatment recommendations for EIA and bronchial hyper-responsiveness in athletes are set forth with special reference to controller and reliever medications. Evidence for lack of improvement of exercise performance by inhaled beta(2)-agonists in healthy athletes serves as a basis for permitting their use. There is a lack of evidence of treatment effects of asthma drugs on EIA and bronchial hyper-responsiveness in athletes whereas extensive documentation exists in treatment of EIA in patients with asthma. The documentation on lack of improvement on performance by common asthma drugs as inhaled beta(2)-agonists with relationship to sports in healthy individuals is of high evidence, level (1+). CONCLUSIONS: Exercise induced asthma should be treated in athletes along same principles as in ordinary asthma patients with relevance to controller and reliever treatment after careful diagnosis. There is very high level of evidence for the lack of improvement in athletic performance by inhaled beta2-agonists.

Exercise-induced asthma, respiratory and allergic disorders in elite athletes: epidemiology, mechanisms and diagnosis: part I of the report from the Joint Task Force of the European Respiratory Society (ERS) and the European Academy of Allergy and Clinical Immunology (EAACI) in cooperation with GA2LEN.

AIMS: To analyze the changes in the prevalence of asthma, bronchial hyperresponsiveness (BHR) and allergies in elite athletes over the past years, to review the specific pathogenetic features of these conditions and to make recommendations for their diagnosis. METHODS: The Task Force reviewed present literature by searching Medline up to November 2006 for relevant papers by the search words: asthma, bronchial responsiveness, EIB, athletes and sports. Sign criteria were used to assess level of evidence and grades of recommendation. RESULTS: The problems of sports-related asthma and allergy are outlined. Epidemiological evidence for an increased prevalence of asthma and BHR among competitive athletes, especially in endurance sports, is provided. The mechanisms for development of asthma and bronchial hyperresponsiveness in athletes are outlined. Criteria are given for the diagnosis of asthma and exercise induced asthma in the athlete. CONCLUSIONS: The prevalence of asthma and bronchial hyperresponsiveness is markedly increased in athletes, especially within endurance sports. Environmental factors often contribute. Recommendations for the diagnosis of asthma in athletes are outlined.

Nimesulide does not interfere with airway responsiveness in allergic asthma.

The clinical use of nonsteroidal anti-inflammatory drugs (NSAIDs) in asthmatic patients is limited by the possibility that these drugs may aggravate asthma by increasing the production of leukotrienes. Nimesulide, an NSAID with a weak inhibitory activity on prostaglandin synthetase, has been hypothesised to be safer than other NSAIDs in asthma. We have recently demonstrated in asthmatics who were allergic to the house dust mite that nimesulide neither alters the bronchial response to allergen nor aggravates the allergen-induced increase in airway responsiveness.

Exercise testing in radiologically-limited, simple pulmonary silicosis.

Forty-five consecutive patients (17 non-smokers and 28 smokers) affected by pulmonary silicosis with limited profusion of radiologic small opacities of "p" type underwent physical examination; resting standard pulmonary function tests (PFT); and progressive, multistage, treadmill-based exercise testing (ET). Results show that, in 78 percent of all patients, maximum oxygen uptake (VO2max) was below 80 percent of predicted, and in most cases this was accompanied by a reduction of anaerobic threshold and/or oxygen pulse. In our group, VO2max predicted was uncorrelated with PFT parameters, symptoms and x-ray picture. No significant differences in response to exercise were observed between smokers and non-smokers. Therefore, exercise was limited by factors other than ventilatory limitation. It is concluded that ET is not more sensitive than PFT for assessing ventilatory impairment in patients with early, simple silicosis, even though it may be valuable for providing information about other sources of exercise limitation.

Assessing the reversibility of airway obstruction.

STUDY OBJECTIVE: To determine whether changes of partial expiratory flow-volume curve (PEFV) and inspiratory capacity (IC) detect functional responses to bronchodilator in patients who do not meet the FEV1 criteria for reversibility of airway obstruction. DESIGN/METHODS: The effects of salbutamol (200 microg by metered-dose inhaler) on lung function were examined in 50 patients with asthma and 28 patients with COPD. Measurements evaluated were FEV1, forced expiratory flow at 30% of control FVC from maximal expiratory flow-volume curve (Vm30), forced expiratory flow at 30% of control FVC from PEFV (Vp30), and IC. On a separate occasion, a representative sample of 26 subjects inhaled placebo to determine the 95% confidence limits (CLs) of each of the parameters. RESULTS: A percent and absolute increment of FEV1 above the upper CL was recorded in 28 patients. Of these, 26 had a percent and absolute increase of Vp30, 21 of Vm30, 9 of FVC, and 11 of IC above the 95% CL. Of the 50 patients who did not have an increase in FEV1 above the 95% CL, 25 had a percent and absolute increase in Vp30, 15 of Vm30, 3 of FVC, and 13 of IC above the 95% CL. On average, the percent and absolute increase Vp30 above the 95% CL significantly identified more responders than every other parameter. CONCLUSION: Increases in maximal flow detected by PEFV and/or changes in IC may be substantially obscured by the effects of inspiration to total lung capacity required for the measurement of FEV1 in patients with chronic bronchoconstriction. Decreases in functional residual capacity (FRC) manifested by an increase of IC occur because, in patients whose FRC is dynamically determined, bronchodilatation that increases maximal flow in the tidal breathing range allows patients to breathe at lower lung volumes. Changes of FEV1 frequently fail to detect significant functional response to bronchodilators in patients with chronic airflow obstruction.

Effect of beta-adrenergic blockade on response to exercise in sedentary and active subjects.

The response to incremental work after placebo and propranolol (80 mg, orally) was studied in 11 sedentary (S) and 11 physically active (PA) healthy subjects. O2 uptake, CO2 output, and minute ventilation were significantly reduced at all or most work rates after propranolol in S subjects, whereas in PA subjects only O2 uptake was occasionally significantly reduced. Maximum work capacity during the propranolol trial was significantly increased by 17% in the S group but was unaltered in the PA group. A subanaerobic threshold constant work test in five sedentary subjects demonstrated that propranolol had no effect on the respiratory response both early and late in exercise. In addition, propranolol did not impair the ability of the respiratory control system to maintain alveolar PCO2 at new set points when external dead space was added during constant load work. We conclude that alterations of gas exchange during incremental work after propranolol administration are related to both physical fitness and type of exercise.

Gas exchange and intrapulmonary distribution of ventilation during continuous-flow ventilation.

In 12 anesthetized paralyzed dogs, pulmonary gas exchange and intrapulmonary inspired gas distribution were compared between continuous-flow ventilation (CFV) and conventional mechanical ventilation (CMV). Nine dogs were studied while they were lying supine, and three dogs were studied while they were lying prone. A single-lumen catheter for tracheal insufflation and a double-lumen catheter for bilateral endobronchial insufflation [inspired O2 fraction = 0.4; inspired minute ventilation = 1.7 +/- 0.3 (SD) 1.kg-1.min-1] were evaluated. Intrapulmonary gas distribution was assessed from regional 133Xe clearances. In dogs lying supine, CO2 elimination was more efficient with endobronchial insufflation than with tracheal insufflation, but the alveolar-arterial O2 partial pressure difference was larger during CFV than during CMV, regardless of the type of insufflation. By contrast, endobronchial insufflation maintained both arterial PCO2 and alveolar-arterial O2 partial pressure difference at significantly lower levels in dogs lying prone than in dogs lying supine. In dogs lying supine, the dependent lung was preferentially ventilated during CMV but not during CFV. In dogs lying prone, gas distribution was uniform with both modes of ventilation. The alveolar-arterial O2 partial pressure difference during CFV in dogs lying supine was negatively correlated with the reduced ventilation of the dependent lung, which suggests that increased ventilation-perfusion mismatching was responsible for the increase in alveolar-arterial O2 partial pressure difference. The more efficient oxygenation during CFV in dogs lying prone suggests a more efficient matching of ventilation to perfusion, presumably because the distribution of blood flow is also nearly uniform.

Effects of aerosol methacholine and histamine on airways and lung parenchyma in healthy humans.

To investigate whether histamine (His) and methacholine (MCh) have different effects on airways and lung parenchyma, 11 healthy subjects were given aerosol MCh until a response plateau was obtained and then two doses of His. At the plateau, forced expiratory volume in 1 s and forced expiratory flow at 40% of vital capacity from partial flow-volume curves were reduced by 19 +/- 3 (SE) and 80 +/- 4%, respectively. Aerosol His decreased forced expiratory volume in 1 s by an additional 12 +/- 1% but left partial forced expiratory flow unchanged. The bronchodilator effect of deep inhalation, as inferred from the ratio of forced expiratory flow from maximal to that from partial flow-volume curves, increased after MCh and plateaued but decreased after His. Quasi-static transpulmonary pressure-volume area determined in seven subjects was unchanged after MCh but was increased by 57 +/- 10% after His. We conclude that adding His after the response to MCh plateaued does not increase the maximal degree of bronchoconstriction but may increase parenchymal hysteresis, thus blunting the bronchodilator effect of deep inhalation. These results suggest that His and MCh have similar effects on airway smooth muscle but different effects on lung tissue properties.