A previous questionnaire interview had revealed that betelnut chewing may aggravate asthma in 61% of asthma patients attending an outpatient clinic at Port Moresby General Hospital; the rest said it had no effect. The aim of the present study was to verify patients' subjective feelings through objective measurements. 7 asthma patients (Group C) who said betelnut aggravated their asthma, 8 asthma patients (Group B) who denied any effect and 8 nonasthmatic, healthy subjects (Group A) were given betelnut with accompanying ingredients and asked to chew as they would usually chew it. Their spirometric forced expiratory volume in the first second (FEV1) readings, heart rate and blood pressure were monitored before and after this challenge. Group A nonasthmatic subjects experienced only minor rises and falls in their FEV1 in response to betelnut chewing. 3 patients in Group B experienced overall rises (mean maximal % rise 25 +/- 19) while 5 patients had overall falls (mean maximal % fall 11 +/- 6). In Group C 1 patient had an overall rise in her FEV1 (maximal rise 10%) while 6 patients had falls (mean maximal % fall 22 +/- 7). In all groups the heart rate increased in response to betelnut. Betelnut chewing caused bronchoconstriction as demonstrated by decreases in FEV1 in a majority of the asthmatic patients studied; hence betelnut may act as a trigger factor for their asthma. In a few others increases in FEV1 were noted, while the rest experienced only minor changes.
Adult ; aged ; Areca - physiology ; Asthma - physiopathology ; Case-Control Studies ; Forced Expiratory Volume - drug effects

Smoking is associated with poor symptom control and impaired therapeutic responses in asthma. A total of 843 patients with asthma were recruited. The patients received treatment for 1 yr according to the severity of their asthma. We compared the forced expiratory volume in 1 sec (FEV1), the ratio of FEV1 to forced vital capaity (FVC), atopy, total IgE, emphysema on high-resolution computed tomography (HRCT), the number of near-fatal asthma attacks, and physiological fixed airway obstruction between the smoking and nonsmoking groups. The study population consisted of 159 (18.8%) current smokers, 157 (18.7%) ex-smokers, and 525 (62.5%) nonsmokers. Although the prevalence of atopy was not different between the smoking and nonsmoking groups, the total IgE was higher among the smokers than the nonsmokers. Compared with the nonsmoking group, the smokers had a lower FEV1 % predicted and forced expiratory flow between 25 and 75% of FVC. A greater prevalence of emphysema and a significantly higher number of asthmatic patients with fixed airway obstruction were detected in the smoking versus nonsmoking group. The 37.5% of asthmatic patients who were former or current smokers showed decreased pulmonary function and increased IgE, emphysema on HRCT, and fixed airway obstruction, indicating that smoking can modulate the clinical and therapeutic responses in asthma.
Airway Obstruction/etiology ; Asthma/complications/*diagnosis/*drug therapy ; Female ; Forced Expiratory Volume/physiology ; Humans ; Immunoglobulin E/analysis ; Male ; Middle Aged ; Pulmonary Emphysema/etiology/radiography ; Respiratory Function Tests ; Respiratory Insufficiency/etiology ; Smoking/*adverse effects ; Tomography, X-Ray Computed

The aim of this study was to investigate relationships between acute exacerbation and Forced Expiratory Volume 1 second (FEV1) improvement after treatment with combined long-acting beta-agonist (LABA) and inhaled corticosteroid (ICS) in patients with chronic obstructive pulmonary disease (COPD). A total of 137 COPD patients were classified as responders or nonresponders according to FEV1 improvement after 3 months of LABA/ICS treatment in fourteen referral hospitals in Korea. Exacerbation occurrence in these two subgroups was compared over a period of 1 yr. Eighty of the 137 COPD patients (58.4%) were classified as responders and 57 (41.6%) as nonresponders. Acute exacerbations occurred in 25 patients (31.3%) in the responder group and in 26 patients (45.6%) in the nonresponder group (P=0.086). FEV1 improvement after LABA/ICS treatment was a significant prognostic factor for fewer acute exacerbations in a multivariate Cox proportional hazard model adjusted for age, sex, FEV1, smoking history, 6 min walk distance, body mass index, exacerbation history in the previous year, and dyspnea scale.Three-month treatment response to LABA/ICS might be a prognostic factor for the occurrence of acute exacerbation in COPD patients.
Adrenal Cortex Hormones/*therapeutic use ; Adrenergic beta-2 Receptor Agonists/*therapeutic use ; Bronchodilator Agents/*therapeutic use ; Budesonide/therapeutic use ; Drug Therapy, Combination ; Female ; Fluticasone/therapeutic use ; Forced Expiratory Volume/drug effects/*physiology ; Formoterol Fumarate/therapeutic use ; Humans ; Male ; Pulmonary Disease, Chronic Obstructive/*drug therapy/physiopathology ; Recurrence ; Republic of Korea ; Salmeterol Xinafoate/therapeutic use ; Smoking ; Spirometry ; Treatment Outcome

BACKGROUNDT lymphocytes and matrix metalloproteinase (MMP) play an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, the details of the mechanisms involved are unclear. The aims of this study were to investigate the changes in interferon-gamma (IFN-gamma), interleukin-4 (IL-4), MMP-9, MMP-12 and tissue inhibitor of metalloproteinase-1 (TIMP-1) levels in a smoke-induced COPD rat model and the therapeutic effects of glucocorticoids and N-acetylcysteine.

METHODSMale Wistar rats were exposed to cigarette smoke for 3.5 months. Budesonide or N-acetylcysteine was given in the last month. Lung function was measured at the end of the study. IL-4 and IFN-gamma levels were then determined in bronchoalveolar lavage fluid and lung tissue samples by enzyme-linked immunosorbent assay. The expression of MMP-9, MMP-12 and TIMP-1 mRNA in lung tissue was determined by RT-PCR.

RESULTSIn comparison with the control group, rats exposed to smoke had a significant increase in IL-4 and MMP-12 levels and a significant decrease in IFN-gamma levels. In addition, the IL-4/IFN-gamma ratio and MMP-12/TIMP-1 ratio were both higher. At the same time, the ratio of forced expiratory volume in 0.3 second to forced vital capacity (FEV(0.3)/FVC) and dynamic compliance (C(dyn)) decreased and expiratory resistance (Re) increased. By measuring pulmonary mean linear intercept and mean alveolar numbers, obvious emphysematous changes were observed in the smoke exposed group. After treatment with budesonide, IL-4 and MMP-12 decreased and IFN-gamma increased. The IL-4/IFN-gamma ratio returned to normal, though the MMP-12/TIMP-1 ratio remained unchanged. FEV(0.3)/FVC was significantly higher and Re was significantly lower than that in untreated smoke exposed rats. No significant differences were found in pulmonary mean linear intercept and mean alveolar numbers. After treatment with N-acetylcysteine, IFN-gamma increased and the IL-4/IFN-gamma ratio decreased. The MMP-12/TIMP-1 ratio remained unchanged. Re and C(dyn) both improved obviously. No significant differences were found in pulmonary mean linear intercept and mean alveolar numbers. Correlation analysis indicated that IL-4 levels in lung tissue correlated negatively with FEV(0.3)/FVC (r = -0.53, P = 0.001), IFN-gamma levels in lung tissue correlated negatively with Re (r = -0.63, P = 0.000) and positively with C(dyn) (r = 0.44, P = 0.009), and that the IL-4/IFN-gamma ratio correlated negatively with FEV(0.3)/FVC (r = -0.44, P = 0.010) and C(dyn) (r = -0.42, P = 0.015) and positively with Re (r = 0.58, P = 0.000). Finally, MMP-12 correlated negatively with FEV(0.3)/FVC (r = -0.36, P = 0.026).

CONCLUSIONSCigarette smoke exposure increases IL-4 levels and decreases IFN-gamma levels. This may be the result of smoke-induced changes in lung function. Budesonide can mitigate the changes in IL-4 and IFN-gamma levels induced by smoke exposure. N-acetylcysteine has no effect on IL-4, but increases IFN-gamma levels and brings the IL-4/IFN-gamma ratio back to normal. Cigarette smoke can also promote MMP-12 gene expression and elevate the MMP-12/TIMP-1 ratio. This effect may play a role in smoke-induced emphysema. Budesonide and N-acetylcysteine do not alter the MMP-12/TIMP-1 ratio in this study when given in the late phase of smoke exposure.

Acetylcysteine ; therapeutic use ; Animals ; Forced Expiratory Volume ; Glucocorticoids ; therapeutic use ; Interferon-gamma ; analysis ; physiology ; Interleukin-4 ; analysis ; physiology ; Lung ; pathology ; physiopathology ; Male ; Matrix Metalloproteinase 12 ; Metalloendopeptidases ; genetics ; Pulmonary Disease, Chronic Obstructive ; drug therapy ; etiology ; physiopathology ; Rats ; Rats, Wistar ; Smoking ; adverse effects ; Tissue Inhibitor of Metalloproteinase-1 ; genetics ; Vital Capacity