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Background Our study aimed to identify preoperative predictors for perioperative allogenic blood transfusion (ABT) in patients undergoing major lung cancer resections in order to improve the perioperative management of patients at risk for ABT. Methods Patients admitted between 2014 and 2016 in a high-volume thoracic surgery clinic were retrospectively evaluated in a cohort study based on a control group without ABT and the ABT group requiring packed red blood cell units within 15 days postoperatively until discharge. The association of ABT with clinically established parameters (sex, preoperative anemia, liver and coagulation function, blood groups, multilobar resections) was analyzed by contingency tables, receiver operating characteristics (ROC) and logistic regression analysis, taking into account potential covariates. Results 60 out of 529 patients (11.3%) required ABT. N1 and non-T1 tumors, thoracotomy approach, multilobar resections, thoracic wall resections and Rhesus negativity were more frequent in the ABT group. In multivariable analyses, female sex, preoperative anemia, multilobar resections, as well as serum alanine-aminotransferase levels, thrombocyte counts and Rhesus negativity were identified as independent predictors of ABT, being associated with OR (95% Confidence interval, p-value) of 2.44 (1.23–4.88, p = 0.0112), 18.16 (8.73–37.78, p Conclusions In patients undergoing major lung cancer resections, multiple independent risk factors for perioperative ABT apart from preoperative anemia and multilobar resections were identified. Assessment of these predictors might help to identify high risk patients preoperatively and to improve the strategies that reduce perioperative ABT.

Background Periodontal disease and lung function impairment were found to be associated with low-grade systemic or local inflammation, and it might be that gingival/periodontal inflammation triggers lung function due to systemic inflammation or the transfer of oral bacteria or its components to the lung. A recent observational study in non-smoking subjects showed that lung volumes and flow rates were significantly reduced by 71–185 ml for severe gingivitis regardless of the adjustment for potential confounders. The result did not show any confounding by smoking, and the association between gingivitis and lower lung function was not modified by systemic inflammation. The designed interventional trial primarily aims to test the hypothesis that gingivitis reduction by optimized daily oral hygiene, professional tooth cleaning and antibacterial chlorhexidine (CHX)-containing mouth rinse improves lung function in terms of forced vital capacity (FVC) by at least 2%. The secondary objective will test the hypothesis that gingivitis reduction improves forced expiratory volume in 1 s (FEV1) and forced expiratory flow at 25–75% of the pulmonary volume (FEF25-75) by at least 2%. Furthermore, the influence of the oral microbiome will be taken into account. Methods The study has to include 120 non-smoking subjects aged between 18 and 30 years with biofilm-induced gingivitis. The chosen “waiting control group design” will compare the immediate intervention group with the delayed intervention group, which serves as a control group. Dental and gingival status, lung function and oral microbiome will be recorded. The intensified preventive intervention—professional tooth cleaning, one-stage full-mouth disinfection with CHX and safeguarding an optimal daily oral hygiene by each subject—cannot be blinded, but the outcome measurement in terms of lung function tests is blind. Discussion This proposed multidisciplinary study has several strengths. Only one previous intervention study with patients with severe periodontitis (mostly smokers) has been performed. It is novel to include non-smoking subjects with mild and potentially reversible oral inflammation. Furthermore, this research is innovative, because it includes evidence-based interventions for gingivitis reduction, standardized measures of the outcome on lung function and oral microbiome and combines expertise from dentistry, lung physiology, oral microbiology and epidemiology/statistical modelling. Trial registration German Clinical Trial Register DRKS00028176. Registered on February 2022.

Objectives Pulmonary perfusion abnormalities are prevalent in patients with chronic obstructive pulmonary disease (COPD), are potentially reversible, and may be associated with emphysema development. Therefore, we aimed to evaluate the clinical meaningfulness of perfusion defects in percent (QDP) using DCE-MRI. Methods We investigated a subset of baseline DCE-MRIs, paired inspiratory/expiratory CTs, and pulmonary function testing (PFT) of 83 subjects (age = 65.7 ± 9.0 years, patients-at-risk, and all GOLD groups) from one center of the “COSYCONET” COPD cohort. QDP was computed from DCE-MRI using an in-house developed quantification pipeline, including four different approaches: Otsu’s method, k-means clustering, texture analysis, and 80th percentile threshold. QDP was compared with visual MRI perfusion scoring, CT parametric response mapping (PRM) indices of emphysema (PRMEmph) and functional small airway disease (PRMfSAD), and FEV1/FVC from PFT. Results All QDP approaches showed high correlations with the MRI perfusion score (r = 0.67 to 0.72, p r = 0.72, p p Emph (r = 0.70 to 0.75, p Emph (mean difference = 35.85 to 40.40) and PRMfSAD (mean difference = 15.12 to 19.68), but in close agreement when combining both PRM indices (mean difference = 1.47 to 6.03) for all QDP approaches. QDP correlated moderately with FEV1/FVC (r = − 0.54 to − 0.41, p Conclusion QDP is associated with established markers of disease severity and the extent corresponds to the CT-derived combined extent of PRMEmph and PRMfSAD. We propose to use QDP based on Otsu’s method for future clinical studies in COPD. Key Points • QDP quantified from DCE-MRI is associated with visual MRI perfusion score, CT PRM indices, and PFT. • The extent of QDP from DCE-MRI corresponds to the combined extent of PRMEmph and PRMfSAD from CT. • Assessing pulmonary perfusion abnormalities using DCE-MRI with QDP improved the correlations with CT PRM indices and PFT compared to the quantification of pulmonary blood flow and volume.

In patients with COPD, it has not been comprehensively assessed whether the predictive value of comorbidities for mortality differs between men and women. We therefore aimed to examine sex differences of COPD comorbidities in regard with prognosis by classifying comorbidities into a comorbidome related to extrapulmonary disorders and a pulmorbidome, referring to pulmonary disorders. The study population comprised 1044 women and 1531 men with the diagnosis of COPD from COSYCONET, among them 2175 of GOLD grades 1–4 and 400 at risk. Associations of comorbidities with mortality were studied using Cox regression analysis for men and women separately. During the follow-up (median 3.7 years) 59 women and 159 men died. In men, obesity, hypertension, coronary artery disease, liver cirrhosis, osteoporosis, kidney disease, anaemia and increased heart rate (HR) predict mortality, in women heart failure, hyperuricemia, mental disorders, kidney disease and increased HR (p Clinical Trial Registration: ClinicalTrials.gov NCT01245933.

Background In hospitalized patients with SARS-CoV-2 infection, outcomes markedly differ between locations, regions and countries. One possible cause for these variations in outcomes could be differences in patient treatment limitations (PTL) in different locations. We thus studied their role as predictor for mortality in a population of hospitalized patients with COVID-19. Methods In a region with high incidence of SARS-CoV-2 infection, adult hospitalized patients with PCR-confirmed SARS-CoV-2 infection were prospectively registered and characterized regarding sex, age, vital signs, symptoms, comorbidities (including Charlson comorbidity index (CCI)), transcutaneous pulse oximetry (SpO2) and laboratory values upon admission, as well as ICU-stay including respiratory support, discharge, transfer to another hospital and death. PTL assessed by routine clinical procedures comprised the acceptance of ICU-therapy, orotracheal intubation and/or cardiopulmonary resuscitation. Results Among 526 patients included (median [quartiles] age 73 [57; 82] years, 47% female), 226 (43%) had at least one treatment limitation. Each limitation was associated with age, dementia and eGFR (p 2, hemoglobin, leucocyte numbers, estimated glomerular filtration rate (eGFR), C-reactive protein (CRP), Interleukin-6 and LDH were predictive for death (p 5 G/l, CRP > 7 mg/l and SpO2 Conclusion In hospitalized patients with SARS-CoV-2, the percentage of patients with treatment limitations was high. PTL were linked to age, comorbidities and eGFR assessed upon admission and strong, independent risk factors for mortality. These findings might be useful for further understanding of COVID-19 mortality and its regional variations. Clinical trial registration ClinicalTrials.gov Identifier: NCT04344171

Komorbiditaten haben einen masgeblichen Einfluss auf die Prognose von Patienten mit COPD. Deutschlands groste COPD-Kohorte COSYCONET liefert Erkenntnisse zu aktuellen Entwicklungen, insbesondere der Rolle von Symptomen und Exazerbationen, der Diagnostik wichtiger Stoffwechselerkrankungen sowie der Blutgasanalyse bei stabilen COPD-Patienten.

Die COPD tritt haufig mit Komorbiditaten auf, insbesondere mit solchen kardiovaskularer Art. Neben den bekannten Einflussen auf den rechten Ventrikel rucken zunehmend prima vista subklinische Veranderungen des linken Ventrikels in den Blick. Die zugrundeliegenden Mechanismen werden derzeit erforscht. In der multizentrischen COSYCONET-Kohorte zeigten sich direkte Einflusse von Obstruktion und Uberblahung auf den linken Ventrikel und die elektrischen Herzachsen im EKG.

Capnovolumetry performed during resting ventilation is an easily applicable diagnostic tool sensitive to airway obstruction. In the present analysis, we investigated in which way capnovolumetric parameters can be combined with basic anamnestic information to support the diagnosis of asthma and COPD. Among 1400 patients of a previous diagnostic study, we selected 1057 patients with a diagnosis of asthma (n = 433), COPD (n = 260), or without respiratory disease (n = 364). Besides performing capnovolumetry, patients answered questions on symptoms and smoking status. Logistic regression analysis, single decision trees (CHAID), and ensembles of trees (random forest) were used to identify diagnostic patterns of asthma and COPD. In the random forest approach, area/volume of phase 3, dyspnea upon strong exertion, s3/s2, and current smoking were identified as relevant parameters for COPD vs control. For asthma vs control, they were wheezing, volume of phase 2, current smoking, and dyspnea at strong exertion. For COPD vs asthma, s3/s2 was the primary criterion, followed by current smoking and smoking history. These parameters were also identified as relevant in single decision trees. Regarding the diagnosis of asthma vs control, COPD vs control, and COPD vs asthma, the area under the curve was 0.623, 0.875, and 0.880, respectively, in the random forest approach. Our results indicate that for the diagnosis of asthma and COPD capnovolumetry can be combined with basic anamnestic information in a simple, intuitive, and efficient manner. As capnovolumetry requires less cooperation from the patient than spirometry, this approach might be helpful for clinical practice.

Ten years after the establishment of health monitoring units (GME) in Bavaria, temporal trends and urban-rural differences in parent-reported respiratory and allergic diseases as well as environmental tobacco smoke (ETS) exposure in preschoolers were analyzed in an explorative manner. Furthermore, associations between diseases and ETS exposure were studied. Parent questionnaires were used as part of the school entrance examination in two cross sectional studies (S1:2004/2005, n (1) = 6350;S2:2012/2013, n (2) = 5052). Temporal trends and urban-rural-differences were tested by X-2 tests. Associations between diseases and exposures were studied using multiple logistic regression analysis. The lifetime prevalence of atopic dermatitis declined from S1-S2 from 12.4 to 11.1 %, whereas those for hay fever, asthma, bronchitis and pseudocroup remained stable. In S1 and S2, bronchitis was less often reported in cities. The other diseases showed no urban-rural differences. The prevalence of children's ETS exposure at home declined from S1-S2 from 14.3 to 7.2 % and was generally higher in cities than in rural regions. There was no positive association between diseases and children's ETS exposure at home. In S2 an association was found between asthma and current parental smoking (OR = 1.60;95 % CI = (1.10-2.32)). The GME provide important data for regional distribution of respiratory and allergic diseases and ETS exposure of preschoolers in Bavaria. The results of the study are important for further development of questionnaires, which will be used in future GME.

Hintergrund Rehabilitation fuhrt bei chronisch obstruktiven Lungenerkrankungen evidenzbasiert zu einer Verbesserung von korperlicher Leistungsfahigkeit, Atemwegssymptomen und Lebensqualitat. Fur berufsbedingte pneumologische Erkrankungen gibt es bislang nur wenige Informationen.

Background Chronic Obstructive Pulmonary Disease (COPD) influences different aspects of patient’s health-related quality of life (HRQL). While disease-specific HRQL instruments focus on symptoms and functional impairments, generic instruments cover a broader view on health. This study compares the generic EQ-5D-3 L and two disease-specific questionnaires (St.-George’s Respiratory Questionnaire (SGRQ-C), COPD Assessment Test (CAT)) in a comprehensive spectrum of COPD disease grades with particular attention on comorbidities and assesses the discriminative abilities of these instruments. Methods Using data from the baseline visit of the German COPD cohort COSYCONET, mean HRQL scores in different COPD grades were compared by linear regression models adjusting for age, sex, education, smoking status, BMI, and low vs. high number of comorbidities or a list of several self-reported comorbid conditions. Discriminative abilities of HRQL instruments to differentiate between COPD grades were assessed by standardized mean differences. Results In 2,291 subjects in COPD GOLD grades 1–4 EQ-5D-3 L utility, EQ-5D VAS, SGRQ, and CAT were found able to discriminate between COPD grades, with some limitations for the EQ-5D utility in mild disease. Both generic and disease-specific HRQL instruments reflected the burden of comorbid conditions. The SGRQ showed the best discrimination between COPD grades and was less influenced by comorbidities, while EQ-5D utility put a higher weight on comorbid conditions. For all instruments, psychiatric disorders and peripheral artery disease showed the strongest negative associations with HRQL. Conclusion All HRQL instruments considered reflect considerable impairment of HRQL in COPD patients, worsening with increasing COPD grade and number of comorbidities. Findings may support clinical assessment, choice of HRQL instrument in future studies, and parameterization of decision-analytic models. Electronic supplementary material The online version of this article (doi:10.1186/s12890-016-0238-9) contains supplementary material, which is available to authorized users.

While malnutrition, especially fat-free mass index (FFMI), is a predictor for mortality in chronic obstructive pulmonary disease (COPD), less information on prevalence and mechanisms is available in patients with chronic respiratory failure (CRF) due to restrictive thoracic diseases (RTD).Cross-sectional study of patients consecutively admitted to an in-patient primary pulmonary centre.One hundred and thirty-two patients (30% RTD; 70% COPD) with CRF and intermittent non-invasive positive pressure ventilation.Malnutrition was quantified by bioelectrical impedance analysis or body mass index (BMI), and its relationship to laboratory, lung function, inspiratory muscle and blood gas parameters and 6-min walking distance (6-MWD) was assessed.Malnutrition in terms of BMI20 kg/m(2) occurred in 16.1% of patients with COPD but none of those with RTD. FFMI17.4 (15.0 in female patients) kg/m(2) was found in 35.4 and 30.7%, respectively. FFMI was correlated with airway obstruction (sR(aw), r = -0.50; FEV(1)/VC, r = -0.28; Por = 0.01 each) and lung hyperinflation (intrathoracic gas volume, r = -0.41; total lung capacity (TLC), r = -0.50; Por = 0.001 each) in COPD, and with lung restriction in RTD (TLC, r=0.40; P=0.011). Furthermore, malnourished patients showed a higher inspiratory load (P (0.1)) and reduced 6-MWD in both groups. In COPD, only hyperinflation and P (0.1) were independently related to FFMI.Malnutrition as indicated by low FFMI was similarly prevalent in patients with CRF and COPD or RTD, but inadequately represented by BMI. The correlations between lung function impairments specific for the disease and FFMI emphasized the link between malnutrition and respiratory mechanical load irrespective of its aetiology.

The present study aimed to investigate, whether short-term experimental exposure to high levels of welding fumes would be capable of exerting acute effects in healthy subjects. Specifically, we assessed cardiovascular function in terms of heart rate variability (HRV) as well as the concentrations of inflammatory mediators and hemostatic proteins in blood as outcome measures. Twenty subjects without a history of airway and cardiovascular diseases were exposed to either control air or welding fume for 1 h on 2 separate days under standardized conditions. The median concentration of the alveolar particle fraction during welding was 3.5 mg/m(3 )(quartiles: 1.4-6.3 mg/m(3); range 1.0-25.3 mg/m(3)). Five hours later a panel of clinical assessments was performed, including HRV measurement and drawing of blood samples. There were no changes in symptom ratings or lung function after welding fume exposure. Exposures did also not differ regarding effects on time- and frequency-domain parameters of HRV. Similarly, blood leukocyte numbers, cell differentials and the blood levels of fibrinogen, C-reactive protein, antithrombin III, factor VIII, von Willebrand factor, ristocetin cofactor, sICAM-1, tumor necrosis factor alpha, interleukin 6, interleukin 8 and epithelial neutrophil activating peptide 78 were not altered by welding fume inhalation. However, there was a significant fall in the level of endothelin-1 (P0.01). In conclusion, the data did not indicate effects of clinical significance of a short-term high-level exposure to welding fumes on HRV or a set of blood hemostatic and acute inflammatory parameters in healthy subjects. The small but statistically significant effect on endothelin levels demonstrated that measurable effects could be elicited even in these individuals. Overall, welding fumes are not likely to exert acute cardiovascular effects in healthy individuals.

As known from studies in animal and human subjects, ozone can exert effects on the immune response including allergic sensitisation and allergen responsiveness. The objective of the present study was to assess the changes in lymphocyte subsets in bronchoalveolar lavage fluid (BALF) after single and repeated ozone exposures. Twenty-three healthy subjects underwent single exposures to 200 ppb ozone or filtered air (FA), as well as repeated exposures to 200 ppb ozone on four consecutive days, each during 4 h of intermittent exercise. Bronchoalveolar lavage was performed 20 h after the single exposure or the last of the repeated exposures. Lymphocytes were identified by sideward scatter and CD45 expression, and their subsets by eight different panels of antibodies. Checksums were calculated to assess the validity of the results. The percentage and the absolute number of lymphocytes, mostly comprising T-lymphocytes (CD2+; overall mean 98.8%), increased after single (P < 0.05; each), but not after repeated ozone exposure, compared with FA (7.4 vs 5.8 vs 6.5%; 680 vs 419 vs 301 × 103). In addition, we observed small but statistically significant changes in the proportions of lymphocyte subpopulations. The percentage of CD4+ lymphocytes increased after single (P < 0.05) and repeated ozone exposure (P < 0.01), whereas the percentage of CD8+ cells decreased after repeated exposure (P < 0.05). The proportion of activated lymphocytes (CD25+) was elevated after repeated, compared with single, ozone exposure (P < 0.01), and the percentages of natural killer (NK) cells were decreased after both single (P < 0.05) and repeated (P < 0.01) exposures. Our data suggest that single but not repeated ozone exposures cause a change in absolute numbers of lymphocytes in BALF, whereas the proportions of lymphocyte subsets are affected by single as well as repeated exposures.

The aim of this study was to investigate the effect of environmental tobacco smoke (ETS) exposure in the evening on inflammatory changes in bronchoalveolar (BAL) and nasal lavage (NAL) fluid.Ten subjects with mild asthma [mean (+/- SD) age, 25 +/- 2 years, FEV1% pred., 93 +/- 6%, PC20FEV1 0.44 x 5.11 mg/ml methacholine] were exposed to ETS (22.4 +/- 1.2 ppm CO) or ambient air (sham) for 3 h (7.00 to 10.00 p.m). Bronchoscopy was performed the following morning at 7.00 a.m. A visual endoscopic score was assessed, and BAL fluids were analyzed for cellular composition and concentrations of histamine, albumin, eosinophilic cationic protein, myeloperoxidase, hyaluronic acid, tryptase, prostanoids and leukotrienes. Nasal lavages were performed 30 min prior to and 30 min after exposures, and NAL fluids were analyzed for histamine, albumin, eosinophilic cationic protein, myeloperoxidase, hyaluronic acid, and tryptase.There was a significant rise in symptoms after ETS exposure compared with sham (P0.05). Spirometric lung function did not change during or after exposure compared with pre-session values. Visual bronchoscopic scoring revealed no significant effect of ETS exposure, nor did BAL cells and mediators or NAL mediators as compared with pre-challenge or post-sham values.In the subjects tested, a 3-h ETS exposure in the evening appeared not to have an inflammatory effect detectable in BAL or NAL fluid.

To study the effect of environmental tobacco smoke (ETS) exposure in the evening on nocturnal changes in airway tone and responsiveness, 17 subjects with mild asthma (mean +/- SD age, 26 +/- 5 years, FEV1% pred., 89 +/- 14%) were exposed to either ambient air (sham) or ETS (20 ppm CO) for 3 h (7:00 to 10:00 p.m.). Seven subjects had a history of ETS-induced respiratory symptoms. Spirometry was performed 2 h before exposure (5:00 p.m.), every 30 min during exposure, and at 11:00 p.m., 3:00 a.m., and 7:00 a.m. The provocative concentrations of methacholine necessary to decrease FEV1 by 20%, PC20FEV1, were assessed at 5:00 p.m., 11:00 p.m., 3:00 a.m., and 7:00 a.m. Compared with pre-exposure measurements, mean FEV1 values during and after ETS exposure were significantly lower than with sham exposure = 0.013 and 0.026). This effect, however, was due to a significant response in single individuals. The higher bronchial responsiveness after ETS than after sham exceeded one doubling concentration in 4, 5, and 4 patients at 11:00 p.m., 3:00 a.m., and 7:00 a.m., respectively. The opposite effect was observed in 2, 2, and 2 patients, respectively. There was no statistically significant mean effect of ETS on airway responsiveness during night; however, there was significant heterogeneity in individual responses (P = 0.0002). Patients with and without a history of ETS-induced symptoms did not show different responses to experimental ETS exposure. In conclusion, our data suggest that in single adult subjects with mild asthma, acute exposure to ETS in the evening can produce a deterioration of airway tone and responsiveness during the night, with wide interindividual variability in the response.

The aim of the reported study was to investigate the reproducibility of the single-cell gel electrophoresis (SCGE) assay in the determination of DNA single-strand breaks (SSBs) and to estimate the statistical requirements when the SCGE assay is used for the detection of genotoxicity in humans. In human peripheral mononuclear leukocytes (PMLs), we repeatedly measured the rate of SSBs after in vitro incubation of cells for 1 h at 4 degrees C in phosphate buffered saline (PBS, basal) or 10 microM or 50 microM H2O2 (induced). Intra-assay variation was determined from cryopreserved PMLs of a single donor. To assess intrasubject and intersubject variation, PMLs of ten healthy, nonsmoking subjects (aged 19-37 years) were tested 5-9 times. Cryopreserved cells revealed a mean coefficient of variation of 18% (PBS) and 7%-9% (H2O2). There were statistically significant differences between individuals in the rate of SSBs after incubation in PBS (P0.01), 10 microM H2O2 (P0.001), and 50 microM H2O2 (P0.001). The range of interindividual variability was 26% for basal and 12%-13% for induced SSBs, and the coefficient of intraindividual variation was 18%-72% (PBS) and 7%-23% (H2O2). Neither basal nor induced rates of DNA damage were related to gender or age. Estimates of the minimum detectable effects were based on these observed sources of variability (power 90%, level of significance 5%, assumed sample size 50). With two different groups, a difference of 31% in basal SSBs or 12% in induced SSBs would be detectable. Repeated measurement within one group could detect a difference of 26% in basal and 9% in induced SSBs. In summary, the SCGE assay appears to be suitable for the detection of single-strand breaks, e.g., in biomonitoring or environmental medicine, and the statistical requirements could be derived from our analysis of the sources of variability.

Background Little is known about the influencing potential of specific characteristics on lung function in different populations. The aim of this analysis was to determine whether lung function determinants differ between subpopulations within Germany and whether prediction equations developed for one subpopulation are also adequate for another subpopulation. Methods Within three studies (KORA C, SHIP-I, ECRHS-I) in different areas of Germany 4059 adults performed lung function tests. The available data consisted of forced expiratory volume in one second, forced vital capacity and peak expiratory flow rate. For each study multivariate regression models were developed to predict lung function and Bland-Altman plots were established to evaluate the agreement between predicted and measured values. Results The final regression equations for FEV1 and FVC showed adjusted r-square values between 0.65 and 0.75, and for PEF they were between 0.46 and 0.61. In all studies gender, age, height and pack-years were significant determinants, each with a similar effect size. Regarding other predictors there were some, although not statistically significant, differences between the studies. Bland-Altman plots indicated that the regression models for each individual study adequately predict medium (i.e. normal) but not extremely high or low lung function values in the whole study population. Conclusions Simple models with gender, age and height explain a substantial part of lung function variance whereas further determinants add less than 5% to the total explained r-squared, at least for FEV1 and FVC. Thus, for different adult subpopulations of Germany one simple model for each lung function measures is still sufficient.

To study the relationship of bronchoconstriction and refractoriness we performed pairs of exercise and hyperventilation tests in 15 patients (mean [SEM] age 28.5 [2.8] years) with a history of exercise-induced asthma. Mean (SEM) maximum specific airway resistance (SRaw) increased during the first exercise test to 33.9 (4.5) and during the second exercise test to 29.8 (5.2) cmH2O x s (n.s.). Mean (SEM) maximum specific airway resistance (SRaw) increased during the first hyperventilation test to 44.0 (5.9) and during the second hyperventilation test to 27.4 (3.3) cmH2O x s (p less than 0.01). Mean maximum bronchoconstriction after corresponding exercise and hyperventilation tests did not differ statistically. There was a significantly larger inter-individual variability in the airway response to hyperventilation (p less than 0.001). From these data we suggest that similar refractoriness can be observed after both exercise and hyperventilation.

In asthmatic patients, short-term exposure to nitrogen dioxide at low concentrations has been reported to result in a nonuniform airway response to various bronchoconstrictive stimuli. We therefore investigated in 11 patients with mild and stable asthma with normal baseline airway tone the effect of 0.25 ppm nitrogen dioxide on the airway response to methacholine. On 2 separate days, the subjects inhaled either 0.25 ppm nitrogen dioxide or filtered air (sham) during 20 min of tidal breathing followed by 10 min of bicycle exercise at room temperature (mean exercise ventilation 30 L/min). Methacholine inhalation tests were performed 1 h after the end of exercise to determine the methacholine concentration necessary to increase SRaw by 100% (PC100SRaw). On a third day, a methacholine challenge was done without previous exposure (control). Mean (SEM) exercise-induced increase of SRaw was 80 (24) % after sham and 82 (25) % after nitrogen dioxide, which was not significantly different (p greater than 0.10). PC100SRaw did not differ on the 3 occasions, geometric mean values (variability of mean) being 0.41 (1.6). 0.41 (1.6), and 0.46 (1.5) mg/ml after sham, nitrogen dioxide, and control, respectively (p less than 0.10). We therefore conclude that in patients with mild and stable asthma short-term exposure to 0.25 ppm nitrogen dioxide during rest and exercise does not increase methacholine responsiveness 1 h after exposure.