Influence of cardiac dysfunction and systemic inflammation on pulmonary function and airway responsiveness in obese subjects.

PURPOSE: Obesity is associated with left ventricular diastolic dysfunction and altered heart rate variability, as well as pulmonary dysfunction. The relationship between asthma and cardiac dysfunction in severely obese subjects is unknown, although it has been hypothesized that cardiac dysfunction may contribute to increase airway hyper-responsiveness (AHR). This study aimed to determine if AHR is associated with left ventricular diastolic dysfunction and heart rate variability in severely obese subjects. METHODS: Sixty-one subjects with severe obesity (BMI ≥35 kg/m2 with comorbidities) completed this study. All subjects completed respiratory questionnaires, spirometry, lung volume measurements, methacholine inhalation test, 24hour Holter monitoring and a complete echocardiography evaluation. Blood samples were obtained for measurement of metabolic markers. Subjects with AHR, defined by a provocative concentration of methacholine inducing a 20% fall in FEV1 (PC20) < 8 mg/ml, were compared with those with no AHR (PC20 ≥8 mg/ml). RESULTS: According to these criteria, 32 subjects had AHR and 29 had no AHR(mean PC201.70 mg/ml and 15.3 mg/ml respectively, p < 0.001). The groups were similar for anthropometric data and comorbidities. Fasting glucose, Hb1Ac, total cholesterol, LDL, triglycerides, Apo-B, C-reactive protein (CRP) and pro-BNP levels were also comparable between groups (p > 0.05). CRP level correlated with PC20 (AHR, r=0.38, p=0.03). Indices of heart rate variability and overall cardiac function were similar in subjects with or without AHR but grade 2 left ventricular diastolic dysfunction was more prevalent in subjects with AHR (p=0.037). CONCLUSIONS: Altered cardiac function, dysglycemia and dyslipidemia do not seem to be significantly associated with AHR in severely obese subjects in contrast to systemic inflammation.

Leptin and adiponectin in obese and non-obese subjects with asthma.

OBJECTIVE: To understand the role of leptin and adiponectin in obese asthmatics. METHODS: We compared serum leptin, adiponectin and sputum leptin levels in 44 non-obese and 44 obese subjects. RESULTS: We found higher serum leptin (P < 0.0001) and lower adiponectin (P = 0.0002) levels in obese asthmatics. Sputum leptin was correlated with body mass index (BMI; r = 0.34, P = 0.03) and serum leptin (r = 0.43, P = 0.005); however, this last correlation was not significant after adjusting for BMI (r = 0.26, P = 0.11). CONCLUSION: Airway inflammation in obese asthmatics may present a different pattern involving leptin. Sputum leptin levels may partially originate from systemic circulation, with other contributing mechanisms.

Adiposity and pulmonary function: relationship with body fat distribution and systemic inflammation.

PURPOSE: Obesity is associated with changes in pulmonary function and increased systemic inflammation. We explored the relationships among adiposity, body fat distribution indices, serum inflammatory markers and pulmonary function. METHODS: This was a post-hoc cross-sectional analysis that included subjects who had previously participated in randomized studies on obesity at our centre. Non-smoking sedentary men (282 subjects, mean age 42) without respiratory diseases were studied. BMI, waist circumference (WC), visceral and subcutaneous adipose tissue (AT), lung residual volume (RV), vital capacity (VC) and expiratory reserve volume (ERV) were measured. Serum leptin, adiponectin, tumor necrosis factor alpha (TNF-α) and high-sensitive C-reactive protein (hs-CRP) levels were measured. RESULTS: In subjects with metabolic syndrome (n=124), percent predicted ERV and RV were significantly associated with BMI (ERV: r=-0.19, p=0.02, RV: r=-0.28, p=0.0007), WC (r=-0.20, p=0.02, r=-0.26, p=0.002), visceral (r=-0.22, p=0.007, r=-0.25, p=0.002) and subcutaneous AT (r=-0.19, p=0.02, r=-0.28, p=0.0007). Percent predicted VC correlated with visceral (r=-0.20, p=0.02) and subcutaneous AT (r=-0.18, p=0.03). Leptin was strongly correlated with BMI (MS/no-MS: r=0.52, p=0.0005/r=0.62, p < 0.0001), WC (r=0.41, p=0.008/r=0.49, p < 0.0001), visceral (r=0.27,p=0.09/0.43, p < 0.0001) and subcutaneous AT (r=0.46, p=0.003/r=0.66, p < 0.0001), while adiponectin levels were associated in subjects with no-MS with WC (r=-0.20, p=0.01), visceral (r=-0.22, p=0.008), and subcutaneous AT (r=-0.17, p=0.05). When adjusted for anthropometric measures, neither ERV, RV nor VC was significantly correlated with serum leptin, adiponectin, TNF-α, or hs-CRP levels. CONCLUSION: These results suggest that the influence of obesity on lung function in healthy subjects is mostly mediated by mechanical factors. Furthermore, not only BMI but also the pattern of fat distribution should be considered when studying associations between adiposity indices and mechanical or inflammatory variables potentially associated with pulmonary function.

Obesity and asthma: a specific phenotype?

BACKGROUND: Obesity is associated with an increased prevalence of asthma, especially in women, and appears to be more severe in the obese. This study aimed to determine if obese subjects have a specific asthma phenotype. METHODS: Forty-four consecutive obese subjects (body mass index [BMI] > or = 30 kg/m(2)) and 44 consecutive nonobese subjects (BMI < 25 kg/m(2)), all with asthma, completed an asthma control questionnaire, and underwent methacholine challenge with symptom perception scores, and sputum induction for differential cell count. BMI, waist circumference, and waist-to-hip ratio also were measured. RESULTS: Despite similar expiratory flows, bronchodilator response, airway responsiveness to methacholine, and symptom perception scores, asthma control was poorer in obese subjects than in nonobese subjects (p = 0.005). Total lung capacity (p = 0.01), expiratory reserve volume (p < 0.0001), functional residual capacity (p < 0.0001), and residual volume (p = 0.006) were lower in obese subjects than in nonobese subjects. Induced-sputum eosinophil and neutrophil counts were similar in both groups, although there was an inverse correlation between sputum eosinophils and waist circumference and a trend for a similar relationship for BMI. Blood serum C-reactive protein (p = 0.009) and fibrinogen (p = 0.0004) levels were higher in obese subjects than in nonobese subjects. CONCLUSION: Obese people with asthma had poorer asthma control than nonobese asthmatics despite similar symptoms perception. Bronchial and systemic inflammatory characteristics and the specific pattern of pulmonary function changes suggest a different phenotype of asthma in these subjects. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT00532363 and NCT00532831.

Lung hyperinflation, perception of bronchoconstriction and airway hyperresponsiveness.

PURPOSE: To compare the influence of underlying airway inflammation and lung hyperinflation on dyspnea during induced bronchoconstriction in subjects with mild asthma (or asymptomatic airway hyperresponsiveness (AAHR). METHODS: Fourteen mild asthmatic and 14 AAHR subjects had methacholine and 5'-adenosine monophosphate (AMP) challenges, and induced sputum analysis. Changes in inspiratory capacity (IC) and respiratory symptom scores were measured after challenges. Perception of respiratory symptoms was recorded on a modified Borg scale. RESULTS: The mean baseline FEV1, IC, mean provocative concentration of methacholine inducing a 20% decrease in FEV1 (PC20), the mean PC20 AMP and median inflammatory cell counts were similar in both groups. After methacholine, mean (+/-SD) reductions in FEV1 were 24.7+/-10.3% in mild asthma and 35.6+/-19.1% in AAHR (P>0.05); reductions in IC were, respectively, 10+/-12% and 24+/-20% (P>0.05); mean breathlessness scores at PC20 were 1.1 in mild asthma and 0 in AAHR P=0.003), and mean chest tightness scores were 1.2 in mild asthma and 0.8 in AAHR (P>0.05). Maximum chest tightness scores following MC correlated with the maximum decrease in IC in mild asthma (rs=0.75,P=0.009) and with the maximum decrease in FEV1 in AAHR (rs=0.60,P=0.04). After AMP, symptom scores were not significantly correlated with decreases in FEV1 or IC. The number of inflammatory cells was not correlated with decreases in IC after methacholine, AMP or with their PC20s, although inflammation was minimal in both groups. CONCLUSION: Lower breathlessness scores in AAHR compared to mild asthma were not explained by differences in lung hyperinflation nor in airway inflammation.

Clinical features and airway inflammation in mild asthma versus asymptomatic airway hyperresponsiveness.

RATIONALE: We still do not know why some subjects with airway hyperresponsiveness (AHR) experience no respiratory symptoms. OBJECTIVES: Our aim was to compare pulmonary function, perception of bronchoconstriction, and airway inflammation in atopic subjects with mild recently diagnosed (<5 years, n=30) or longer-standing (5 years or more, n=30) symptomatic asthma in comparison with atopic subjects with asymptomatic AHR (n=27). METHODS: All subjects had measurements of expiratory flows, PC(20) methacholine, perception of breathlessness and induced sputum cell differential, eosinophil cationic protein and alpha(2)-macroglobulin levels. RESULTS: Compared with the other groups, PC(20) was significantly lower in longer-standing asthma and perception score for breathlessness at 20% fall in FEV(1) was lower in asymptomatic subjects. Markers of airway inflammation were similar in all groups. There were no significant correlations between sputum eosinophils, alpha(2)-macroglobulin and/or eosinophil cationic protein levels and FEV(1), FVC or PC(20) in either group. CONCLUSION: Subjects with mild asthma or asymptomatic AHR are similar in regard to induced sputum markers of airway inflammation. Although perception of bronchoconstriction was slightly lower in asymptomatic subjects, additional factors are probably involved to explain why they report no respiratory symptoms. Further studies are needed to determine why these last are asymptomatic.

Deep inspiration avoidance and methacholine response in normal subjects and patients with asthma.

BACKGROUND: Deep inspiration (DI) avoidance and time intervals between inhalation and measurement of FEV1 may influence methacholine challenges. OBJECTIVES: (1) To compare the degree of airway response to methacholine when the initial FEV1 measurements are obtained either 30 s or 3 min after inhalation, (2) to evaluate a simplified method to study the influence of DI avoidance before inhalation on the fall in FEV1, and (3) to determine if methacholine has a cumulative effect. PARTICIPANTS/METHODS: Twenty-five patients with asthma and 21 normal subjects without asthma. Four methacholine inhalation tests (MITs) were performed: two standard tidal-breathing MITs, with the first FEV1 measured 30 s (test A) and 3 min (test B) after the end of inhalation; a single-dose MIT, using the last concentration from test B, with no control of DI and the first FEV1 obtained 3 min after inhalation (test C); and an identical single-dose MIT preceded by 20-min of DI avoidance (test D). We compared the provocative concentration of methacholine causing a 20% fall in FEV1 (PC20) from tests A and B (aim 1), the percentage fall in FEV1 from tests C and D (aim 2), and the percentage fall in FEV1 from tests B and C (aim 3). RESULTS: Mean PC20 values from tests A and B were 1.5 mg/mL and 1.0 mg/mL (p = 0.002) in patients with asthma, and 69.8 mg/mL and 29.9 mg/mL (p < 0.0001) in control subjects, respectively. The mean falls in FEV1 for tests C and D were 22.0% and 24.5% (p > 0.05) in patients with asthma, and 22.1% and 38.9% (p = 0.0005) in control subjects, respectively. The mean falls in FEV2 for tests B and C were 30.2% and 22.0% (p = 0.01) in patients with asthma, and 27.5% and 22.1% (p > 0.05) in control subjects, respectively. CONCLUSIONS: In both groups, the longer the time interval between the end of inhalation and the first FEV2 measurement, the greater the fall in FEV2 (lower PC20). DI avoidance before inhalation does not enhance the fall in FEV2 in subjects with asthma, while it does in control subjects. Methacholine has a slight cumulative effect that is significant in patients with asthma (p = 0.007).

Deep inspiration avoidance and airway response to methacholine: Influence of body mass index.

OBJECTIVE: To evaluate the effects of deep inspiration avoidance response to methacholine inhalation in 23 nonobese (body mass index between 18 kg/m2 and 30 kg/m2) and 27 obese (body mass index 30 kg/m2 or greater), nonatopic, nonasthmatic normal subjects. METHODS: Each subject had four methacholine challenges. In tests A and B, the first postmethacholine forced expiratory volume in 1 s (FEV1) was measured at 30 s and 3 min postinhalation, respectively; tests C and D were single-dose tests (using the final dose of test B), with the first postmethacholine FEV1 being obtained at 3 min, without (test C) or with (test D) 20 min of deep inspiration avoidance before inhalation. RESULTS: The mean provocative concentrations inducing a 20% fall in FEV1 on tests A and B were 80.6 mg/mL and 28.5 mg/mL (P<0.0001) in nonobese subjects, respectively, and 56.3 mg/mL and 21.5 mg/mL (P<0.0001) in obese subjects, respectively. No significant differences were observed in test A or B between control and obese subjects. Mean falls in FEV1 for tests C and D were 20.3% and 40.0% (P=0.0003) in nonobese subjects, respectively, and 18.5% and 23.6% (P>0.05) in obese subjects, respectively. CONCLUSIONS: As previously observed in patients with asthma, the present study found that nonasthmatic obese subjects had no increase in the fall in FEV1 after deep inspiration avoidance before methacholine, whereas nonobese subjects did, suggesting that obesity alters airway function. No significant changes were found between groups for symptom perception.

Asthma and sleep apnea in patients with morbid obesity: outcome after bariatric surgery.

BACKGROUND: Asthma and sleep apnea syndrome (SAS) are frequently reported in obese patients. The authors determined the prevalence of asthma and SAS in morbidly obese patients and the effect of biliopancreatic diversion with duodenal switch (BPD-DS) on these conditions. METHODS: 398 patients were evaluated for bariatric surgery in a university-affiliated tertiary care center. All patients completed a written questionnaire on asthma and SAS before BPD-DS. In addition, 139 patients also completed a questionnaire on their general health status, including asthma and SAS, 2 years after the procedure. RESULTS: For the cohort of 398 patients, the prevalence of self-reported asthma was 30.4% and that of SAS, 32.2%. No significant association was found between asthma and SAS diagnosis (P =0.10). Significant relationships were observed between the diagnosis of asthma and age, hip circumference, waist/hip ratio, weight and BMI of the patients as well as between a diagnosis of SAS and gender, waist circumference, hip circumference, waist/hip ratio, weight and BMI. 2 years after surgery (mean BMI was reduced from 51.4 to 30.5 kg/m(2)), asthma was reported improved in 79.3% of patients and SAS was improved in all but one with this condition; among 29 SAS patients using CPAP before surgery, only 4 were still using this treatment after 2 years. CONCLUSION: The prevalence of asthma and SAS is high in the morbidly obese population and is associated with markers of obesity. We found no association between the diagnosis of asthma and SAS diagnosis in this population. BPD-DS improved self-reported severity of asthma and SAS symptoms.

Prevalence of respiratory symptoms in an athlete population.

This study aimed to look at the prevalence and type of respiratory symptoms experienced by athletes and to assess the possible influence on the perception of symptoms of training duration and environment. A group of 698 athletes (107 with diagnosed or self-reported asthma) filled out a questionnaire on their respiratory condition. They exercised either in cold air (n = 176), dry air (n = 384), humid air (n = 95) or mixed dry and humid air (n = 43). Past exercise-related symptoms reported by athletes were breathlessness (48.7%), phlegm production (22.8%), wheezing (15.6%), cough (15.2%), and chest tightness (7.4%). Only 25% of asthmatic athletes reported having current exercise-induced symptoms of breathlessness, 21.7%, wheezing and 17.4%, chest tightness; current exercise-induced symptoms of breathlessness, wheezing or chest tightness were also reported, respectively, in 38.9%, 3.6% and 2.7% of athletes without a diagnosis of asthma. The perception of exercise-induced symptoms was not influenced by the duration of training or environment. In conclusion, (1) a minority of asthmatic athletes report troublesome respiratory symptoms with exercise, (2) breathlessness is not more frequently reported in asthmatic athletes than in those without such diagnosis while cough and wheezing are more common in asthmatic subjects and (3) the prevalence of respiratory symptoms is independent of training environment and duration of training.

Comparative prevalence of asthma in different groups of athletes: a survey.

BACKGROUND: The type of air predominantly inhaled during training seems to play an important role in the development of airway hyperresponsiveness in athletes; however, this factor has not been evaluated for asthma. OBJECTIVE AND PATIENTS: To compare the prevalence of self-reported and/or physician-diagnosed asthma among four groups of athletes categorized according to the type of air predominantly inhaled during training: cold air (n=176), dry air (n=384), humid air (n=95), and mixed dry and humid air (n=43). METHOD: Self-administrated questionnaires were used. RESULTS: One hundred seven (15.3%) of the 698 athletes reported having asthma; of these 107 athletes, 92 had physician-diagnosed asthma. No significant differences were found for the prevalence of asthma: 15.9% (cold air), 15.4% (dry air), 12.6% (humid air) and 18.6% (mixed dry and humid air), respectively (P>0.05). Furthermore, no significant differences were observed among the groups for the prevalence of confirmed atopy, cold/flu or respiratory infections (all P>0.05), except for the prevalence of hay fever, which was significantly lower among athletes of the dry air group (P=0.04). Athletes having a first-degree relative with asthma did not have a higher prevalence of asthma than those who did not (P>0.05). CONCLUSION: The prevalence of asthma was not significantly different among the four groups of athletes and it was not associated with a family history of asthma.

Effect of bariatric surgery on airway response and lung function in obese subjects with asthma.

BACKGROUND: Obesity is a risk factor for self-reported asthma and makes asthma management more difficult. The effects of bariatric surgery on asthma in severely obese subjects remain to be documented. METHODS: In this prospective study, 12 asthmatic patients with severe obesity were evaluated before, 6 and 12 months after bariatric surgery. Each had methacholine inhalation tests, measures of expiratory flows and lung volumes, measurements of C-reactive protein and questionnaires on asthma medication, asthma symptoms and co-morbid conditions. Eleven severely obese patients with asthma (considered as controls) underwent the same evaluations. Primary endpoint was airway responsiveness to methacholine and secondary endpoints were lung volumes and markers of systemic inflammation. RESULTS: Mean body mass index decreased from 51.2 to 34.4 kg/m(2) twelve months post-surgery. Mean PC(20) methacholine improved from 0.84 to 6.2 mg/ml (P < 0.001); FEV(1), FVC, FRC, FRC/TLC and ERV all improved (P ≤ 0.006). C-reactive protein decreased from 8.6 to 1.7 mg/L (P < 0.001) Asthma symptoms total score was significantly reduced (P = 0.03) and asthma medication needs decreased, ten patients being able to stop all asthma drugs. No significant changes of these parameters from baseline were observed in asthmatic controls. Improvements in airway responsiveness and lung volumes happened in parallel and correlated with reductions of body mass index (r = 0.58, P = 0.049), C-reactive protein levels (r = -0.74, P = 0.004). CONCLUSION: Airway responsiveness, lung volumes and asthma severity/control markedly improved with weight loss following bariatric surgery in severely obese patients.

Gender differences in the prevalence of airway hyperresponsiveness and asthma in athletes.

BACKGROUND: Although athletes have a high prevalence of airway hyperresponsiveness (AHR) and asthma, little is known about possible gender differences in regard to these features. We looked at the comparative prevalence of AHR, physician-diagnosed asthma and respiratory symptoms during exercise in female (F) and male (M) athletes. METHOD: A retrospective analysis was done on 2 groups of athletes: Group 1 (n=100) taking part in a study on the prevalence of AHR to methacholine (PC(20)<16mg/ml) and Group 2 (n=698), taking part in a provincial survey on the prevalence of physician-diagnosed asthma. Subjects from both groups filled the same questionnaire on respiratory symptoms during exercise (breathlessness, wheezing and chest tightness). RESULTS: In Group 1, prevalence of AHR was significantly higher in female (60%) compared with male (21.5%, p<0.0001) athletes despite a similar prevalence of physician-diagnosed asthma (F: 17.1%, M: 15.4%, p>0.05). Respiratory symptoms during exercise were more frequently reported in females (37.1%, M: 16.9%, p=0.02); however, when corrected for the PC(20), this difference became non-significant. In Group 2, the prevalence of physician-diagnosed asthma was not different between genders (F: 12.5%, M: 14%, p>0.05) but respiratory symptoms during exercise were more often reported in female (19.4%) than in male (12.2%, p=0.01) athletes. CONCLUSIONS: This analysis shows a higher prevalence of AHR and exercise-induced respiratory symptoms in female compared to male athletes, but a similar prevalence of physician-diagnosed asthma. This suggested that the increase in respiratory symptoms in female athletes failed to translate into a higher prevalence of physician-diagnosed asthma.

Benefits of low-dose inhaled fluticasone on airway response and inflammation in mild asthma.

RATIONALE: Current guidelines suggest that asthma should be controlled with the lowest dose of maintenance medication required. OBJECTIVES: To evaluate the effects of a low dose of inhaled corticosteroid compared to a placebo, on airway inflammation and responsiveness in patients with mild symptomatic asthma. METHODS: In this randomized double-blind, placebo-controlled, parallel group study, we looked at the influence of inhaled fluticasone propionate 250 microg/day for 3 months followed by 100 microg/day for 9 months on airway inflammation and methacholine responsiveness in non-smoking subjects with mild allergic asthma. Subjects were evaluated at baseline and 3, 6, 9 and 12 months after treatments; a 2-week evaluation of respiratory symptoms and peak expiratory flow measurements was done before each visit. RESULTS: Fifty-seven subjects completed the 3-month study period. Airway responsiveness, expressed as the PC20 methacholine, increased by 0.27 and 1.14 doubling concentrations, respectively, in placebo-treated (n=33) and in fluticasone-treated (n=24) asthmatic subjects (p=0.03). An additional improvement in PC20 up to 2.16 doubling concentrations was observed in the fluticasone-treated group during the 9-month lower-dose treatment (p=0.0004, end of low-dose period compared with placebo). Sputum eosinophil counts decreased after 3 months of fluticasone 250 microg/day compared with placebo (p<0.0001) and remained in the normal range during the 9-month lower-dose treatment. Respiratory symptoms and peak expiratory flows did not change significantly throughout the study in both groups. CONCLUSION: In mild asthma, keeping a regular minimal dose of ICS after asthma control has been achieved, may lead to a further reduction in airway responsiveness and keep sputum eosinophil count within the normal range.

Lower airway inflammatory responses to high-intensity training in athletes.

PURPOSE: There is an increased prevalence of asthma and airway hyperresponsiveness in elite athletes, particularly in swimmers. High intensity exercise may induce airway inflammation and subsequent remodelling in these subjects. Our aim was to evaluate the effects of high-intensity training on induced-sputum cell populations in elite athletes. METHODS: Swimmers and runners with hyperresponsive airways (SH and RH), defined by a provocative concentration of methacholine inducing a 20% decrease in FEV1 (PC20) <16 mg/ml or with normoresponsive airways (PC20 > 16 mg/ml; SN, RN) to methacholine were enrolled. The mean PC20 was 2.27 mg/ml in SH (n=12), 32.2 in SN (n=10), 3.25 in RH (n=10) and 41.5 in RN (n=13). All athletes had two induced sputum analyses at one- to two-week intervals in random order: after a period of 72 hours without training, 24 hours after a training session. RESULTS: PC20 was unchanged after training. The median % neutrophils and eosinophils in groups SH, SN, RH, and RN, respectively, were 26.5-1.6, 8.6-0.3, 28.0-0.03 and 25.5-0.1 before and 45.0-0.5, 31.1-0.4, 54.0-0.6 and 48.3-0.3 after training. While the magnitude of the increase in neutrophils was similar for all groups, it reached statistical significance (pre-post-training) only in the SH group (P = 0.039). CONCLUSION: A one-hour session of high-intensity training was associated with an increase in airway neutrophils among hyperresponsive swimmer athletes, while airway responsiveness remained unchanged in all groups.

Are questionnaires on respiratory symptoms reliable predictors of airway hyperresponsiveness in athletes and sedentary subjects?

This study aimed at determining the frequency of respiratory symptoms in high-level athletes and whether respiratory questionnaires are reliable predictors of airway hyperresponsiveness (AHR) in this population compared with control subjects. One hundred high-level athletes exercising in different conditions of ambient air (dry, humid, cold or mixed dry and humid) and 50 sedentary control subjects answered four question sets on exercise-induced symptoms of postnasal drip (Q1), breathlessness, chest tightness and wheezing (Q2), and cough (Q3). Another question set (Q4) evaluated the self-description of nociceptive sensations associated with respiratory symptoms. Methacholine inhalation tests were performed in all subjects to obtain a 20% fall in forced expiratory volume in 1 second (PC20). AHR could be detected by questionnaires in 37 of 44 (84%) subjects with a PC20 < 8 mg/mL. Sensitivity to detect AHR varied between the different subgroups of athletes with each of the question sets; however, no significant differences in sensitivity were observed between the groups of athletes and controls except for Q3 (P=.007), in which athletes exercising in cold air reported more exercise-induced cough. Q2 had a better specificity (83%) than Q3 (77%) and Q4 (64%). Combined question sets revealed that three swimmers, two triathletes, and two controls, who answered negatively to all question sets, had a PC20 < 8 mg/mL. Questionnaires on symptoms and on associated nociceptive sensations may help to detect AHR as well in athletes and controls, although for some subgroups of athletes such as swimmers and triathletes and in some controls, false negative questionnaires can be observed and AHR underreported.