T helper 17 cells and related cytokines after allergen inhalation challenge in allergic asthmatics.

BACKGROUND: T helper (Th)17 cells may play a role in allergic asthma. This study assessed the effect of allergen inhalation challenge on circulating Th17 cells and related cytokines in allergic asthmatics. METHODS: Peripheral blood mononuclear cells were collected from 16 atopic asthmatics before and 24 h after allergen challenge, as well as from 10 atopic nonasthmatics and 10 normal controls. Cells were stained for Th17 cytokines and their receptors (IL-17A, IL-17F, IL-21, IL-22, IL-17R, and IL-23R) using flow cytometry. Cytokine concentrations from cell culture supernatants were quantified using a multiplex assay for IL-17A, IL-17F, IL-21, IL-22, and IL-23. RESULTS: At baseline, asthmatics had a higher percentage of circulating Th17 cells (1.2 ± 0.5%) compared to normal controls (0.9 ± 0.66%, p < 0.001) but not compared to atopic nonasthmatics (1.13 ± 0.5%). There was a significant increase in Th17 cells in asthmatics after allergen challenge to 1.55 ± 0.4% (p < 0.05) and a trend toward significance in IL-17R expression from 3.4 ± 4.3 to 6.86 ± 6.84% after allergen challenge (p = 0.06). There was also a significant reduction in IL-21-positive cells following allergen challenge from 3.46 ± 1.85 to 2.33 ± 1.37% (p < 0.001). There were no significant differences in IL-17F, IL-22 and IL-23R expression. The concentration of IL-17A in culture supernatant was significantly higher in asthmatics compared to normal controls and IL-17A significantly increased 24 h after allergen challenge. CONCLUSIONS: The increase of Th17 cells and IL-17A in atopic asthma after allergen inhalation challenge suggests a possible role for Th17 in allergen-induced airway responses.

The effects of particle size on measurement of airway hyperresponsiveness to methacholine.

BACKGROUND: The effect of particle size on methacholine provocation concentration causing a decrease in forced expiratory volume of 1 second (FEV1) of 20% (PC20) is debatable. OBJECTIVE: To evaluate the functional effects of 3 different particle size nebulizers on methacholine PC20. METHODS: Participants were randomly assigned to have 3 methacholine challenges on 3 separate days. Nebulizer mass median aerodynamic diameter (MMAD) was provided by manufacturers. The Wright nebulizer (MMAD, 1.0 µm), Aeroneb (MMAD, 3 µm), and Aeroneb (MMAD, 5 µm) were calibrated, and the nebulizer outputs were calculated to administer 0.26 mL of methacholine over 120, 112, and 83 seconds, respectively. After each inhalation, spirometry was performed and the test was terminated when the PC20 was achieved. RESULTS: Eight nonsmoking patients with mild asthma (4 male and 4 female) completed the study. The mean (SD) age was 25 (13.9) years, and the mean (SD) baseline FEV1 was 88% (11.3%). Patients using the Aeroneb (MMAD, 5 µm) nebulizer had the lowest PC20 (bronchoconstricted at lowest methacholine concentration), with a PC20 geometric mean of 0.62 mg/mL compared with patients using the Aeroneb (MMAD, 3.0 µm), who had a PC20 of 1.76 mg/mL, and patients using the Wright nebulizer (MMAD, 1.0 µm), who had a PC20 of 6.32 mg/mL. There was a significant difference in PC20 across all particle sizes (P < .001). The pairwise differences revealed a P < .001 between 3 µm and 1 µm and between 5 µm and 1 µm and a P = .008 between 5 µm and 3 µm. CONCLUSION: Our results reveal a variability in methacholine PC20 using 3 different nebulizers, despite adjusting the nebulizers' outputs. Our results are consistent with the previous reports, which recommended using larger particle size nebulizers in the assessment of airway hyperresponsiveness in asthma. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00529477.

Comparison of changes in lung function measured by plethymography and IOS after bronchoprovocation.

AIM: Lung function tests are essential for the diagnosis and management of bronchial asthma. Impulse oscillation (IOS) system is an alternative way to measure lung mechanics for some patients. We investigated the relative sensitivities of IOS, body plethysmography and spirometry in detecting allergen- and methacholine-induced bronchoconstriction. METHOD: Twenty-two subjects had single allergen inhalation and 8 subjects had 3 methacholine challenges. The tests were stopped when FEV1 fell by 20%. Lung function was measured using IOS (R5, R20, R5-R20, X5, AX, fres), plethysmography (sRaw, sGaw, FRC, lung volumes) and spirometry (FEV1, FVC, PEF, FEF50%) during inhalation challenges, and expressed as percent change from pre-challenge baseline. RESULTS: All subjects were non-smoking adults with mild allergic asthma. Following allergen challenges, the most sensitive IOS index was R5-R20 and the most sensitive plethysmography and spirometry measurements were sRaw, sGaw and FEF50%. Following methacholine challenge the most sensitive IOS index was AX, the most sensitive plethysmography measurement was sRaw. Overall, IOS (R5-R20, AX, X5Hz) proved to be more sensitive than plethysmography and spirometry measurements following allergen-induced and methacholine-induced bronchoconstriction. CONCLUSION: Our result shows that IOS is more sensitive than other lung function tests following allergen and methacholine challenge. In addition, IOS can act as an alternative measurement technique of airway resistance and obstruction in patients where manoeuvres involved in plethysmography and spirometry prove difficult to perform.

Effectiveness of pulmonary rehabilitation in restrictive lung disease.

BACKGROUND: Pulmonary rehabilitation is effective in improving exercise endurance and quality of life in chronic obstructive pulmonary disease (COPD). However, the efficacy of pulmonary rehabilitation in restrictive lung disease has not been extensively studied. METHODS: Forty-six patients with restrictive lung disease (35 interstitial lung diseases, 11 skeletal abnormalities) were admitted to a pulmonary rehabilitation program; 26 completed the 8-week program and 15 were followed to a 1-year reassessment. Fifteen noncompliant patients were excluded and 1 patient with interstitial lung disease died at 8 weeks. Pulmonary function tests, exercise endurance, quality of life (Chronic Respiratory Disease Questionnaire, St. George's Respiratory Questionnaire, Hospital Anxiety and Depression scale and dyspnea) were measured at baseline, 8 weeks, and 1 year. RESULTS: Exercise endurance (treadmill) improved at 8 weeks (mean improvement, 10.2 +/- 7.4 minutes) and at 1 year (mean improvement, 8.7 +/- 12.2 minutes). Shuttle test improved at 8 weeks (mean improvement, 27.2 +/- 75.9 m) but not at 1 year. Patients using long-term oxygen therapy (LTOT) had a better improvement in the treadmill test (P < .01) at 8 weeks compared with those not using LTOT. Thirty-three percent of patients failed to complete the program. There was significant improvement in dyspnea and quality of life in Chronic Respiratory Disease Questionnaire, St. George's Respiratory Questionnaire, and Hospital Anxiety and Depression scale for depression at 8 weeks compared with baseline; there was a sustained significant reduction in hospital admission days noted at 1-year postrehabilitation (P < .05). CONCLUSIONS: Pulmonary rehabilitation is effective in improving exercise endurance and the quality of life and in reducing hospital admissions in this small group of patients with significant restrictive lung disease. The relatively large dropout number suggests that a standard chronic obstructive pulmonary disease program may not be ideal for patients with restrictive lung disease.