Bronchial hyperresponsiveness, airway inflammation, and airflow limitation in endurance athletes

BACKGROUND: Whereas a high prevalence of bronchial abnormalities has been reported in endurance athletes, its underlying mechanisms and consequences during exercise are still unclear. STUDY OBJECTIVES: The purpose of this study was to assess the following: (1) bronchial responsiveness to methacholine and to exercise; (2) airway inflammation; and (3) airflow limitation during intense exercise in endurance athletes with respiratory symptoms. DESIGN: Cross-sectional observational study. SETTING: Lung function and exercise laboratory at a university hospital. PATIENTS AND MEASUREMENTS: Thirty-nine endurance athletes and 13 sedentary control subjects were explored for the following: (1) self-reported respiratory symptoms; (2) bronchial hyperresponsiveness (BHR) to methacholine and exercise; (3) airflow limitation during intense exercise; and (4) bronchial inflammation using induced sputum and nitric oxide (NO) exhalation. RESULTS: Fifteen athletes (38%) showed BHR to methacholine and/or exercise in association with bronchial eosinophilia (mean [+/- SD] eosinophil count, 4.1 +/- 8.5% vs 0.3 +/- 0.9% vs 0%, respectively), higher NO concentrations (19 +/- 10 vs 14 +/- 4 vs 13 +/- 4 parts per billion, respectively), a higher prevalence of atopy, and more exercise-induced symptoms compared with non-hyperresponsive athletes and control subjects (p < 0.05). Furthermore, airflow limitation during intense exercise was observed in eight athletes, among whom five had BHR. Athletes with airflow limitation reported more symptoms and had FEV1, FEV1/FVC ratio, and forced expiratory flow at midexpiratory phase values of 14%, 9%, and 29%, respectively, lower compared with those of nonlimited athletes (p < 0.05). CONCLUSION: BHR in endurance athletes was associated with the criteria of eosinophilic airway inflammation and atopy, whereas airflow limitation during exercise was primarily a consequence of decreased resting spirometric values. Both BHR and bronchial obstruction at rest with subsequent expiratory flow limitation during exercise may promote respiratory symptoms during exercise in athletes.     

Bronchial hyperresponsiveness in adolescents with long-term asthma remission: importance of a Family history of bronchial hyperresponsiveness

BACKGROUND: The mechanisms responsible for bronchial hyperresponsiveness (BHR) in symptomatic asthma include genetic predisposition and airway inflammation, but the causes of BHR in adolescents with asthma remission are poorly understood. It has been shown that BHR in adolescents with asthma remission was not reduced by prolonged treatment with inhaled corticosteroids, in contrast to the BHR of symptomatic asthma. OBJECTIVE: The aim of this study was to investigate whether family history of BHR may contribute to the persistence of BHR in asthma remission during adolescence. METHODS: One hundred twenty-six adolescents with long-term asthma remission (neither symptoms nor any medication used during the previous 2 years) and their parents underwent a methacholine inhalation test. The provocative concentration of methacholine causing a 20% fall in FEV(1) (PC(20)) and the bronchial responsiveness (BR) index were calculated for each individual. RESULTS: Sixty-nine adolescents (54.8%) were found to have persisting BHR (PC(20) < 18 mg/mL). The frequency of BHR and the BR index were significantly higher in parents (n = 138) of the BHR-persisting group (28.3% and 1.150 +/- 0.103, respectively [mean +/- 1 SD]) than in parents (n = 114) of BHR-nonpersisting group (16.7% [p = 0.030] and 1.124 +/- 0.088 [p = 0.029], respectively). Furthermore, adolescents (n = 56) with at least one BHR-positive parent were found to have a higher frequency of BHR (66.1% vs 45.7%, p = 0.023) and a higher BR index (1.244 +/- 0.090 vs 1.204 +/- 0.082, p = 0.011) than adolescents (n = 70) with non-BHR parents. CONCLUSION: Our results suggest that adolescents in asthma remission are more likely to have BHR when there is a family history of BHR. Further studies are needed to examine the possible involvement of genetic factors in the BHR of adolescents in asthma remission.     

Bronchial responsiveness after human heart-lung transplantation

We evaluated bronchial responsiveness to inhaled albuterol (salbutamol), ipratropium bromide, methacholine, and propranolol in eight heart-lung transplant (HLT) recipients 2.3 +/- 1.5 months (mean +/- SD) (range, 1 to 4.5 months) after HLT. All patients had a restrictive ventilatory defect but none had airflow limitation (FEV1/FVC = 0.93 +/- 0.05) (range, 0.86 to 0.97). Specific airway conductance (sGaw) improved significantly with both albuterol (p less than 0.01) and ipratropium bromide (p less than 0.01) but FEV1 did not. Only one HLT patient had bronchoconstriction with propranolol, whereas all but one were hyperresponsive to methacholine. Prior inhalation of ipratropium bromide blocked the response to methacholine (p less than 0.005). Serial methacholine provocation tests performed in seven long-term survivors of HLT 24.6 +/- 16.0 months (range, 12 to 51 months) after HLT revealed no time-dependent evolution of bronchial hyperresponsiveness to methacholine. Limited maximal airway narrowing to methacholine was seen in five HLT recipients who showed a 29 +/- 4 percent (range, 23 to 35 percent) fall in FEV1 compared with two patients who did not achieve a plateau with a 47 percent and 63 percent fall in FEV1, respectively. These results further our understanding of bronchial responsiveness in the denervated transplanted lung. The findings of stable hyperresponsiveness to methacholine over a prolonged time interval, limited maximal airway narrowing to methacholine, and blockade of methacholine hyperresponsiveness by ipratropium bromide support the concept of denervation hypersensitivity of muscarinic receptors.     

Bronchial hyperreactivity in patients with mitral stenosis before and after successful percutaneous mitral balloon valvulotomy

OBJECTIVES: We aimed to identify the bronchial response to inhaled methacholine in patients with mitral stenosis (MS) and to clarify whether or not the bronchial hyperreactivity (BHR) is reversible after percutaneous mitral balloon valvulotomy (PBMV). PATIENTS AND SETTING: Thirty patients with MS and 28 age-matched healthy control subjects were prospectively evaluated with pulmonary function tests and methacholine challenge. The productive concentration of methacholine causing 20% decrease in FEV(1) (PC(20)) was calculated and used as a parameter of bronchial responsiveness. BHR was defined as a PC(20) < 8 mg/mL. Mean pulmonary artery pressure (PAP) and mean pulmonary capillary wedge pressure (PCWP) were recorded in all patients through a Swan-Ganz balloon-tipped catheter. Sixteen patients underwent PMBV, and a methacholine test was repeated after each procedure. RESULTS: Bronchial response to methacholine was significantly increased in patients with MS, so that 53% of them had BHR, whereas all control subjects were nonresponders. The PC(20) was closely correlated with the PAP (r = - 0.777; p < 0.001), PCWP (r = - 0.723; p < 0.001), and mitral valve area (MVA; r = 0.676; p < 0. 001). Balloon valvulotomy was successfully performed in all of the 16 patients, and the cardiac parameters (MVA, PAP, and PCWP) significantly improved after the procedure. In contrast, no significant changes were shown in pulmonary function test variables (total lung capacity, vital capacity [VC], FEV(1), and FEV(1)/VC). Although significant improvement was observed in the mean PC(20) values (from 4.97 +/- 5.24 to 7.47 +/- 6.96 mg/mL; p = 0.0006), BHR was completely eliminated in only one patient. CONCLUSIONS: Our data shows that BHR is fairly common among patients with MS, and severity of bronchial responsiveness is significantly correlated with the severity of MS. Moreover, PMBV leads to significant reduction in pulmonary congestion and a consequent improvement in BHR.     

Bronchial hyperresponsiveness and exhaled nitric oxide in patients with cardiac disease

BACKGROUND: Increased concentrations of exhaled nitric oxide (NO) correlate with increased airway inflammation and measurement of exhaled NO is a noninvasive method for the management of bronchial asthma. In various cardiac diseases, bronchial hyperresponsiveness is observed, as is bronchial asthma. However, there have been few studies on the relationship between exhaled NO and bronchial responsiveness in cardiac diseases. OBJECTIVE: The aim of this study was to clarify the association between exhaled NO and bronchial hyperresponsiveness in patients with cardiac disease. METHODS: We measured expired NO and bronchial responsiveness to inhaled methacholine in 19 patients with cardiac diseases and 17 with bronchial asthma. We divided the cardiac disease patients into two groups according to their bronchial responsiveness to inhaled methacholine: BHR(+) group consisted of 12 patients with bronchial hyperresponsiveness and BHR(-) group consisted of 7 patients without bronchial hyperresponsiveness. RESULTS: The concentration of exhaled NO in the asthmatic patients was significantly higher than that in the BHR(+) and BHR(-) groups (142.0 +/- 17.0, 33.6 +/- 6.4 and 42.3 +/- 10.3 ppb, respectively, p < 0.01). There was no significant difference in exhaled NO between BHR(+) and BHR(-) groups. There were also no significant differences in the parameters of bronchial hyperresponsiveness between the cardiac BHR(+) and bronchial asthma groups. These results indicate that bronchial hyperresponsiveness in patients with cardiac diseases is not a consequence of eosinophilic inflammation or of exhaled NO. CONCLUSION: We conclude that bronchial hyperresponsiveness in patients with cardiac diseases can occur independently of NO production.     

Indomethacin does not inhibit the ozone-induced increase in bronchial responsiveness in human subjects

Exposure of human subjects to sufficiently high levels of ozone can result in reversible changes in lung function (restrictive in nature) and increases in nonspecific airway responsiveness. Several studies have implicated products of cyclooxygenase metabolism in the mediation of these changes. The purpose of this study was to determine if indomethacin (a cyclooxygenase inhibitor) would alter the changes in the ozone-induced increase in responsiveness to methacholine or the ozone-induced decrease in lung function. Thirteen male subjects underwent three randomly assigned 2-h exposure to 0.4 ppm ozone with alternating 15-min periods of rest and exercise on a cycle ergometer (30 L/min/m2, body surface area). For the 4 days before each of the exposures, the subjects received either indomethacin (150 mg/day) or placebo, or no modification. Of the 13 subjects, only seven had both detectable indomethacin serum levels on the indomethacin Study Day and a significant increase in bronchial responsiveness to methacholine on the No Medication Day. For this group of seven subjects, we found that indomethacin did not alter the ozone-induced increase in bronchial responsiveness to methacholine (decrease in PC100SRaw for the different study days: no medication, -78.4 +/- 5.3% [mean +/- SEM]; placebo, -48.9 +/- 12.2%; indomethacin, -64.5 +/- 6.3%; p greater than 0.2), although indomethacin did attenuate the ozone-induced decrease in lung function. The decrease in the FEV1 for the different study days was as follows: no medication, -20.7 +/- 5.0% (mean +/- SEM); placebo, -19.2 +/- 6.3%; indomethacin, -4.8 +/- 3.7% (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Atopic status and level of bronchial responsiveness in parents of children with acute bronchiolitis.

To examine whether children with a genetic predisposition to asthma are more likely to be afflicted with bronchiolitis, we studied 122 parents of infants who were hospitalized with the diagnosis of acute bronchiolitis (index group) and 120 parents of children who had never suffered from this disease (control group). The parents underwent bronchial challenge testing with methacholine and skin prick testing with common airborne allergens, and gave blood specimens for measurement of serum total IgE. There was no difference in atopic status, as assessed by the prevalence of atopy (at least one positive response to the allergens tested) or by serum total IgE levels, between index and control parents. The prevalence of bronchial hyperresponsiveness (BHR) (concentration of methacholine causing a 20% reduction in forced expiratory volume in 1 sec [PC20] < 18 mg/mL) was higher in index parents than in control parents (17.2% vs. 7.5%, p = 0.02). Bronchial responsiveness (BR) index was significantly higher in index parents than in control parents (1.135 +/- 0.088 vs. 1.104 +/- 0.071, p < 0.01). Parents of children who were hospitalized with acute bronchiolitis showed a higher level of BR, but not atopy. This suggests that in terms of BHR, there may be a genetic predisposition to the development of bronchiolitis.     

Comparison of percentage fall in FVC at the provocative concentration of methacholine causing a 20% fall in FEV(1) between patients with asymptomatic bronchial hyperresponsiveness and mild asthma

BACKGROUND: A significant proportion of individuals who have no symptoms of asthma or other respiratory diseases show bronchial hyperresponsiveness (BHR). BHR is usually assessed by measuring the provocative concentration of methacholine causing a 20% fall in FEV(1) (PC(20)). The percentage fall in FVC at the PC(20) (DeltaFVC) has been suggested to reflect maximal airway response and to be a more useful index of disease severity in asthma than PC(20). The aim of this study was to investigate whether asymptomatic BHR would differ from symptomatic BHR with regard to DeltaFVC. METHODS: Methacholine bronchial challenge tests were conducted in children with no past or current symptoms of asthma, allergic rhinitis, or other respiratory diseases, who were identified among siblings of children with asthma. Forty-three children with asymptomatic BHR (PC(20) < 16 mg/mL) were recruited, and 43 children with mild asthma who were matched for age, sex, and PC(20) were selected (mild asthma group). The DeltaFVC on methacholine concentration-response curves was retrospectively analyzed in the two groups. RESULTS: There were no differences in the frequency of atopy, blood eosinophil counts, serum IgE levels, and spirometric values between the asymptomatic BHR and mild asthma groups. Mean (+/- SD) DeltaFVC was significantly (p = 0.005) lower in the asymptomatic BHR group (14.5 +/- 3.6%) than in the mild asthma group (16.9 +/- 4.3%). CONCLUSIONS: Our results suggest that children with asymptomatic BHR have a lower level of maximal airway response than mild asthmatics with a similar degree of BHR. This may be a possible explanation for the lack of symptoms in subjects with asymptomatic BHR.     

Effect of cold air exposure and exercise on nonspecific bronchial reactivity

Exercise and eucapnic hyperventilation with cold air can produce bronchoconstriction in asthmatic subjects, but their enhancement of nonspecific bronchial reactivity remains unclear. We studied the effect of submaximal exercise and cold air exposure on bronchial reactivity to methacholine in a normal control group (n = 10) and in subjects with bronchial asthma (n = 17). Bronchial provocation testing was performed to determine the provoking dose (PD35) of methacholine that caused a 35 percent decrease in specific airway conductance (Gaw/VL) in the two groups. Each subject was studied on three different occasions to determine the PD35 to methacholine on a control day, after ten minutes of submaximal exercise, and after a 30-minute exposure to cold air. Methacholine challenge was performed after the Gaw/VL had returned to the baseline values. In the normal group, neither cold air exposure nor exercise challenge had any significant effect on baseline Gaw/VL, whereas in the asthmatic group, both stimuli caused 20 percent and 15 percent decreases in Gaw/VL, respectively (p less than .05). Mean +/- SD control PD35 was 6.1 +/- 11.6 breath units in the asthmatic group, which decreased to 2.2 +/- 2.8 after exercise and 3.0 +/- 5.0 breath units after cold air exposure (p less than .05). In the normal group, control PD35 was 73 +/- 32 breath units, which was not different from PD35 values of 64 +/- 75 and 52 +/- 64 breath units after exercise and cold air exposure, respectively (p = NS). These data suggest that submaximal exercise and cold air exposure enhance nonspecific bronchial reactivity in asthmatic but not in normal subjects.     

Bronchial hyperresponsiveness in subjects with gastroesophageal reflux

BACKGROUND: The relationship between gastroesophageal reflux (GER) and asthma has been widely studied in the last years. GER may interfere with airway reactivity and aggravate or even induce asthma. OBJECTIVE: To assess the prevalence of bronchial hyperresponsiveness (BHR) in patients with GER disease with a view to judging the potential influence of GER on BHR. METHODS: 30 patients with GER disease and no clinical evidence of asthma and 30 normal subjects underwent a methacholine bronchial challenge. The methacholine concentration that caused a 20% fall in the FEV(1) (PC20) was used to assess bronchial responsiveness. RESULTS: In the GER group 11 subjects of the 30 studied showed a PC20 methacholine equal to or less than 8 mg/ml while in the control group only 2 subjects had a PC20 methacholine equal to or less than 8 mg/ml (p < 0.01; ANOVA test). CONCLUSIONS: Subjects with GER had a greater increase in airway reactivity when inhaling methacholine compared to disease-free normal subjects.     

The lack of the bronchoprotective and not the bronchodilatory ability of deep inspiration is associated with airway hyperresponsiveness

In healthy subjects, deep inspiration (DI) acts both as a bronchodilator and a bronchoprotector. The latter is impaired in asthmatics. We have now evaluated whether the lack of bronchoprotection is related to bronchial hyperresponsiveness (BHR), and whether the bronchodilatory effect is also lost in asthmatics. Ten healthy subjects (PC20 > 75 mg/ml), 12 asthmatics with moderate to severe BHR (PC20 < 1 mg/ml), 14 asthmatics with mild to borderline BHR (1 < PC20 < 25 mg/ml), and 10 rhinitics with mild to borderline BHR (1 < PC20 < 25 mg/ml) underwent single-dose methacholine provocations inducing at least 20% reduction in FEV1 after 20 min of DI inhibition. To measure the bronchodilatory effect, DIs were taken immediately after the postmethacholine spirometry, and lung function was again tested. To measure the bronchoprotective effect, DIs were taken before the administration of spasmogen. All four groups achieved the same reductions in FEV1 and FVC, in the absence of deep breaths (analysis of variance [ANOVA], p = 0.49). Only healthy subjects showed bronchoprotection (percent bronchoprotection, mean +/- SEM; healthy: 79 +/- 4.0; asthmatics with moderate to severe BHR: 12 +/- 14.5; asthmatics with mild to borderline BHR: -7 +/- 19.7; rhinitics with mild to borderline BHR: 2 +/- 14.0). In contrast, DIs were able to partially reverse bronchial obstruction in all four groups, albeit percent bronchodilation in healthy subjects was somewhat stronger. The dissociation between bronchoprotection and bronchodilation suggests that the two effects involve different mechanisms.     

Induced sputum analysis in asymptomatic young adults with bronchial hyperresponsiveness to methacholine

BACKGROUND AND OBJECTIVES: BHR is a clinical feature of asthma and factors crucial to the development of BHR remain to be elucidated. Asymptomatic BHR also occurs in the general population. This study examined the prevalence of asymptomatic BHR in a population of young Japanese atopic individuals to identify whether airway inflammation is present in asthmatic patients but not in asymptomatic subjects with BHR. METHODS: Fifty atopic volunteers (aged 18-23 years) without lower respiratory symptoms were recruited and their bronchial responsiveness to methacholine was measured in order to categorize them into two groups, those with BHR (PC(20) below 8 mg/mL) and those without BHR. We evaluated the inflammatory cell profiles and measured IL-5 and IL-13 levels in sputum from subjects of each group by ELISA. Results were compared with those for young adult asthmatic patients. RESULTS: In the young atopic group, 17 subjects (34.0%) exhibited BHR. Compared with asthmatic patients sputum from asymptomatic subjects with BHR contained significantly lower numbers of eosinophils (P < 0.001) and had significantly lower levels of IL-5 (P = 0.088) and IL-13 (P = 0.032). There were no significant differences in each inflammatory parameter between the two asymptomatic groups. CONCLUSIONS: In young adult atopic subjects with asymptomatic BHR, airway inflammation does not necessarily play a determining role in the development of BHR to methacholine itself, though it might be an important factor in the onset of asthma.     

Increased fine particle deposition in women with asymptomatic nonspecific airway hyperresponsiveness

Previous studies suggest that lung function tests using monodisperse aerosols can help to identify early stages of lung diseases. We investigated intrapulmonary particle loss and aerosol bolus dispersion-a marker of convective gas transport-in 32 women with asymptomatic nonspecific bronchial hyperresponsiveness (BHR) compared with 60 women without BHR. Deposition of inhaled particles (0.9 micrometer mass median aerodynamic diameter [MMAD]) was calculated from particle losses of inhaled aerosol boluses consisting of di-2-ethylhexyl sebacate droplets. Convective gas mixing was assessed by the aerosol bolus dispersion method. Women with BHR, nonsmokers as well as smokers, showed significantly increased deposition of aerosol particles (nonsmokers: 45.6 +/- 8.8%; smokers: 49.2 +/- 5.4%; mean +/- SD) compared with the control group of female nonsmokers without BHR (38.2 +/- 9.1%; mean +/- SD) (p < 0.01). Aerosol bolus dispersion values showed a trend for higher values in subjects with BHR (nonsmokers: 572 +/- 122 cm3; smokers: 587 +/- 85 cm3) compared with the control group (542 +/- 88 cm3) (p = 0.2). Also, the maximal expiratory flow at 25% vital capacity (MEF25) showed a trend for decreased values in nonsmokers with BHR compared with nonsmokers without BHR (64 +/- 16% of predicted versus 78 +/- 24% of predicted; p = 0.03). These results suggest that deposition of inhaled particles (0.9 micrometer MMAD) administered by the aerosol bolus technique is a sensitive index of peripheral lung injury that is usually not assessable by conventional methods.     

Lack of bronchial hyperresponsiveness to methacholine and to isocapnic dry air hyperventilation in heart/lung and double-lung transplant recipients with normal lung histology. The Paris-Sud Lung Transplant Group.

To investigate whether survivors of heart/lung and double-lung transplantations have normal or increased nonspecific bronchial responsiveness, nine heart/lung and four double-lung transplant recipients with normal lung histology underwent methacholine challenge and voluntary isocapnic dry air hyperventilation (VIH) in a randomized order at a mean time of 14.8 +/- 12.1 months after surgery. Transplant recipients were compared with 10 normal subjects and 11 patients with mild asthma. Asthmatic patients had a mean provocative concentration of methacholine inducing a 20% fall (PC20) in FEV1 of 3.4 +/- 3.6 mg/ml (SD). Seventy seven percent of the transplant recipients and 70% of the normal subjects had PC20 superior to 32 mg/ml. The percentage fall from baseline FEV1 after VIH was 12.6 +/- 10.4% in asthmatic patients as compared with 1.9 +/- 2.9% in transplant recipients (p = 0.002) and 0.45 +/- 1.2% in normal subjects (p = 0.001). The decrease in FEV1 after VIH was similar in transplant recipients and normal subjects (p = 0.14). These results show that heart/lung or double-lung transplant recipients with normal lung histology have a normal response to nonspecific bronchial stimulation.     

Assessment of magnesium status in patients with bronchial asthma.

To elucidate the contribution of magnesium to bronchial hyperreactivity in patients with stable bronchial asthma, magnesium concentrations in serum (S-Mg), erythrocytes (R-Mg), and lymphocytes (L-Mg) were measured in 25 patients with bronchial asthma (BA group) and 9 age-matched healthy subjects (control group). A parenteral magnesium loading test, a continuous low-dose magnesium infusion of 0.2 mEq/kg over 4 hr, was performed in 10 of 25 asthmatic patients and in the control group. R-Mg was significantly lower in the BA group than in the control group (4.96 +/- 0.47, 6.13 +/- 0.62 mEq/L, p < 0.001, respectively), although S-Mg (2.4 +/- 0.1, 2.4 +/- 0.2 mg/dL) and L-Mg (1.28 +/- 0.26, 1.15 +/- 0.13 microg/mg/protein) were not significantly different between the two groups. Magnesium deficiency in total body stores was revealed in 40% of patients (4/10 patients) and 11% of control subjects (1/9 subjects) by parenteral magnesium loading test. The ratio of magnesium retention to urinary excretion through the parenteral magnesium loading test showed a significant inverse correlation with R-Mg (r = -0.78, p < 0.01). Bronchial reactivity to inhaled methacholine had a significant inverse correlation with R-Mg (r = -0.42, p < 0.05). We conclude that 40% of asthmatic patients demonstrated magnesium deficiency, and that the low magnesium concentration in erythrocytes reflects decreased magnesium stores in patients with bronchial asthma.     

Effects of specific immunotherapy in allergic rhinitic individuals with bronchial hyperresponsiveness

Allergic rhinitis can be associated with bronchial hyperresponsiveness (BHR), and carries an increased risk for the development of asthma. The aim of this study was to evaluate the ability of specific immunotherapy (SIT) to reduce the progression of allergic rhinitis to asthma and prevent the associated increase in BHR. Forty-four subjects monosensitized to Dermatophagoides pteronyssinus, with perennial rhinitis and BHR to methacholine, were randomly assigned to receive SIT or placebo in a double-blind study conducted over a period of 2 yr. After 1 yr of treatment, a 2.88-fold increase in the provocative dose of methacholine producing a 20% decrease in FEV(1) (PD(20)FEV(1)) was recorded in the SIT-treated group (95% confidence interval [CI]: 3.98- to 2.09-fold; p < 0.001), with a further increase to fourfold at the end of Year 2 (95% CI: 2.9- to 5.7-fold; p < 0.001). At the end of the study, the methacholine PD(20)FEV(1) was within the normal range in 50% of treated subjects (p < 0.0001), and was significantly higher in this group than in the group receiving placebo (p < 0.0001). In contrast, no changes in methacholine PD(20)FEV(1) were found in the placebo group throughout the study. Although 9% of subjects given placebo developed asthma, none of those treated with SIT did. This study suggests that SIT, when administered to carefully selected, monosensitized patients with perennial allergic rhinitis, reduces airway responsiveness in subjects with rhinitis, and may be an appropriate prophylactic treatment for rhinitic patients with hyperreactive airways.     

Bronchial inflammation and airway responses to deep inspiration in asthma and chronic obstructive pulmonary disease

RATIONALE: Deep inspirations provide physiologic protection against airway narrowing in healthy subjects, which is impaired in asthma and chronic obstructive pulmonary disease (COPD). Airway inflammation has been suggested to alter airway mechanics during deep inspiration. OBJECTIVES: We tested the hypothesis that the number of bronchial inflammatory cells is related to deep inspiration-induced bronchodilation in asthma and COPD. METHODS: In a cross-sectional study, three modified methacholine challenges were performed in 13 patients with mild, persistent asthma, 12 patients with mild to moderate COPD, and 12 healthy control subjects. MEASUREMENTS AND MAIN RESULTS: After a 20-minute period of deep inspiration avoidance, inhalation of methacholine was followed by either one or five deep inspirations, or preceded by five deep inspirations. The response to deep inspiration was measured by forced oscillation technique. Inflammatory cells were counted within the lamina propria and airway smooth muscle area in bronchial biopsies of patients with asthma and COPD. The reduction in expiratory resistance by one and five deep inspirations was significantly less in asthma (mean change+/-SD: -0.5+/-0.8 and -0.9+/-1.0 cm H2O/L/s, respectively) and COPD (+0.2+/-1.1 and +0.4+/-1.0 cm H2O/L/s, respectively) as compared with healthy subjects (-1.5+/-1.3 and -2.0+/-1.2 cm H2O/L/s, respectively; p=0.05 and p=0.001, respectively). In asthma, this was related to an increase in mast cell numbers within the airway smooth muscle area (r=0.73; p=0.03), and in CD4+ lymphocytes in the lamina propria (r=0.61; p=0.04). CONCLUSIONS: Inflammation in the airway smooth muscle bundles and submucosa of bronchial biopsies is positively associated with impaired airway mechanics during deep inspiration in asthma, but not in COPD. Clinical trial registered with www.clinicaltrials.gov (NCT OO279136).     

Effect of aging on the relationship between asthma severity and bronchial hyperresponsiveness in children with asthma.

An association between asthma and bronchial hyperresponsiveness (BHR) has been demonstrated. It is possible that the relationship between asthma severity and BHR in children with asthma is different in infants and in adolescents. The aim of this study is therefore to evaluate the effect of aging on the relationship between the severity of asthma and BHR in children with asthma. We measured BHR in 386 subjects ranging from 2 to 20 years of age. The subjects consisted of 323 children with asthma (boys:girls = 193:130, mean age 9.7 years) and 63 age-matched controls (boys:girls = 25:38, mean age 8.2 years). BHR was measured using the methacholine inhalation challenge by measuring the transcutaneous oxygen pressure (tcPO2) in children less than 6 years of age (Dmin-PO2) and by measuring the respiratory resistance (Rrs) in children 6 years of age and older (Dmin-Rrs). Throughout the whole age range, both the Dmin-PO2 and Dmin-Rrs in each asthma severity group were higher than those in the controls. In the asthmatics aged 2-5 years, the Dmin-PO2 levels in the mild asthma group were higher than those in the moderate and severe asthma groups (p < 0.001, p < 0.001, respectively), and the Dmin-PO2 levels in the moderate asthma group were also higher than those in the severe asthma group. This tendency was also found in the age ranges of 6-9 years and 10-13 years. In the asthmatics aged 14-20 years, the Dmin-Rrs levels were not significantly different among the three groups. Taken together, these data show that aging has an effect on the relationship between the severity of asthma and BHR during childhood and that BHR may not be the sole determinant for the severity of asthma in adolescence.     

Bronchial hyperreactivity and spirometric impairment in patients with seasonal allergic rhinitis

We previously demonstrated in a group of patients with perennial allergic rhinitis alone, impairment of spirometric parameters and high percentage of bronchial hyperreactivity (BHR). Thus, the present study aimed at evaluating a group of subjects suffering from seasonal allergic rhinitis alone to investigate the presence of spirometric impairment and BHR both during and outside the pollen season. METHODS: One-hundred rhinitics sensitized to pollen allergens only were evaluated during and outside the pollen season. Spirometry and methacholine bronchial challenge were performed. RESULTS: Four rhinitics showed impaired values of FEV1 without referred symptoms of asthma during the pollen season. FEF 25-75 values were impaired in 17 rhinitics during the pollen season and in 11 rhinitics outside the pollen season (P<0.05). Fifty-four patients showed positive methacholine bronchial challenge both during and outside the pollen season. PD20/FEV1 methacholine was lower during the pollen season than outside (P<0.05). In BHR positive patients, reduced values of FVC (P<0.05), FEV1 (P<0.05), and FEF 25-75 (P<0.01) were significantly demonstrated in comparison with BHR negative rhinitics. There was a relationship between BHR degree and FEF 25-75 values only during the pollen season (P<0.001). CONCLUSIONS: This study evidences that an impairment of spirometric parameters may be observed also in patients with seasonal allergic rhinitis alone during the pollen season. A high percentage of these patients had BHR. A close relationship between upper and lower airways is confirmed also in the model of pollen allergy. Thus, a careful evaluation of lower airways should be performed also in those patients with seasonal allergic rhinitis alone.     

Increased frequency of asymptomatic bronchial hyperresponsiveness in nonasthmatic patients with food allergy.

Subclinical inflammation in gut mucosa has been demonstrated in bronchial asthma suggesting the whole mucosal system is involved in allergic diseases. The presence of subclinical bronchial involvement was assessed by nonspecific bronchial hyperresponsiveness (BHR) in nonasthmatic patients with food allergy (FA). BHR was studied in 35 patients with various manifestations of FA without food-induced asthma. Sixteen had a previous history of asthma and/or rhinitis to aeroallergens (group A), whereas 19 patients (group B) did not. BHR was defined by a provocative dose causing a 20% fall in forced expiratory volume in one second of (PC20) <8 mg.mL(-1) of methacholine. Asymptomatic BHR occurred frequently in nonasthmatic patients with FA (10 of 19, 53%); this did not significantly differ from patients with FA and a previous history of asthma and/or rhinitis to aeroallergens (13 of 16, 81%). PC20 was significantly lower in group A (1.84+/-0.53 mg.mL(-1)) than in group B (3.35+/-0.74 mg.mL(-1); p<0.05). The number of patients with positive skin tests to aeroallergens was similar between groups. Sequential evaluation, performed 1 year after initial evaluation, in 7 nonasthmatic patients (group B) demonstrated a similar level of BHR. The present study demonstrated that BHR is a frequent finding in nonasthmatic patients with food allergy which may be due, at least in part, to a subclinical inflammatory process in the bronchi.