Relationship between levels of secreted phospholipase A2 groups IIA and X in the airways and asthma severity.

Background Secreted phospholipase A(2) (sPLA(2) ) may be important mediators of asthma, but the specific sPLA(2) s involved in asthma are not known. Objective To evaluate sPLA(2) group IIA, V, and X proteins (sPLA(2) -IIA, sPLA(2) -V, and sPLA(2) -X) in bronchoalveolar lavage (BAL) fluid, BAL cells, and airway epithelial cells of subjects with and without asthma, and examine the relationship between the levels of specific sPLA(2) enzymes and airway inflammation, asthma severity, and lung function. Methods The expression of sPLA(2) -IIA, sPLA(2) -V, and sPLA(2) -X in BAL cells and epithelial brushings was assessed by qPCR. The levels of these sPLA(2) proteins and sPLA(2) activity with and without group II and group X-specific inhibitors were measured in BAL fluid from 18 controls and 39 asthmatics. Results The airway epithelium expressed sPLA(2) -X at higher levels than either sPLA(2) -IIA or sPLA(2) -V, whereas BAL cells expressed sPLA(2) -IIA and sPLA(2) -X at similar levels. The majority of sPLA(2) activity in BAL fluid was attributed to either sPLA(2) -IIA or sPLA(2) -X. After 10-fold concentration of BAL fluid, the levels of sPLA(2) -X normalized to total protein were increased in asthma and were associated with lung function, the concentration of induced sputum neutrophils, and prostaglandin E(2) . The levels of sPLA(2) -IIA were elevated in asthma when normalized to total protein, but were not related to lung function, markers of airway inflammation or eicosanoid formation. Conclusions and Clinical Relevance These data indicate that sPLA(2) -IIA and sPLA(2) -X are the major sPLA(2) s in human airways, and suggest a link between the levels of sPLA(2) -X in the airways and several features of asthma.

Conjugated linoleic acid improves airway hyper-reactivity in overweight mild asthmatics.

BACKGROUND: Conjugated linoleic acids (CLA) are naturally occurring fatty acids that have multiple biological properties including the regulation of metabolic, proliferative and immune processes. OBJECTIVE: The aim of this study was to investigate the efficacy and safety of CLA as a dietary supplement in mild asthma. METHODS: This was a prospective, randomized, double-blind, placebo-controlled study. Twenty-eight adult subjects (aged 19-40 years) with mild asthma (FEV(1)>70% predicted) were randomized to CLA 4.5 g/day or placebo for 12 weeks in addition to usual treatment. On average, subjects were overweight with a mean body mass index (BMI) of 27.9 kg/m(2). RESULTS: Subjects in the CLA group had a significant improvement in airway hyperresponsiveness (AHR) at week 12 compared with week 0 [PC(20) 6.6 (2.1) mg/mL vs. 2.2 (0.7) mg/mL; P<0.05]. The CLA group had a significant reduction in weight and BMI compared with placebo and this was associated with a reduction in leptin/adiponectin ratio. There were no differences in systemic cytokine levels, induced sputum cell counts, quality-of-life scores or adverse events. CONCLUSIONS: CLA treatment as an adjunct to usual care in overweight mild asthmatics was well tolerated and was associated with improvements in AHR and BMI.

The timed walk test as a measure of severity and survival in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a relentlessly progressive disease with a median survival of approximately 3 yrs. Measurements of airflow and lung volumes at rest are generally used to monitor the clinical course in this disorder. This study was designed to determine if a modified version of the 6-min walk test, called the timed walk test, accurately characterises disease severity and survival in IPF. The study population consisted of 28 patients with well-characterised progressive IPF. The timed walk test and concurrent measures of disease severity were assessed at baseline. Participants were prospectively followed for > or =4 yrs to determine the relationship between parameters of the timed walk test and survival. There were strong correlations between the end-exercise saturation and walk-velocity parameters of the timed walk test and diffusing capacity, and arterial oxygen tension at rest. In univariate Cox proportional-hazards models, end-exercise saturation, change in saturation with exercise, walk distance and walk velocity were associated with survival. In unadjusted logistic regression models, odds of death at 2 yrs were associated with the same parameters. In conclusion, the timed walk test relates to disease severity and long-term outcome in progressive idiopathic pulmonary fibrosis.

Inhaled IFN-gamma for persistent nontuberculous mycobacterial pulmonary disease due to functional IFN-gamma deficiency.

Pulmonary infection with nontuberculous mycobacteria (NTM) in previously healthy human immunodeficiency virus-seronegative individuals is difficult to treat. Recently, functional interferon (IFN)-gamma deficiency has been identified in individuals susceptible to this disease. Treatment with inhaled IFN-gamma for NTM pulmonary disease associated with functional IFN-gamma deficiency has not been previously described. In this study, the IFN-gamma pathway was characterised in an individual who had progressive NTM pulmonary infection, despite appropriate multidrug antibiotic therapy, and 10 healthy controls. Levels of IFN-gamma and tumour necrosis factor-alpha in whole blood were assessed before and after incubation with lipopolysaccharide, heat-killed Escherichia coli, heat-killed Staphylococcus aureus and phorbol myristate acetate/ionomycin. The coding regions of interleukin (IL)-12, IL-18 and the IL-12 receptor were sequenced using nested primers. IFN-gamma1b (100 microg.dose(-1)) was administered to the affected individual by ultrasonic nebuliser 3 days.week(-1) for 3 months. In vitro whole blood production of IFN-gamma with and without physiological stimuli was consistent with functional IFN-gamma deficiency in the affected individual. There was no evidence of mutation in the coding regions of IL-12p35, IL-12p40, IL-12Rbeta1 and IL-18 in the affected individual. Treatment with inhaled IFN-gamma resulted in rapid and sustained clearance of the organism from the airways and stabilisation of lung function. In conclusion, inhaled interferon-gamma can be effective for the treatment of nontuberculous mycobacteria pulmonary disease associated with functional interferon-gamma deficiency.

Aerobic conditioning in mild asthma decreases the hyperpnea of exercise and improves exercise and ventilatory capacity.

STUDY OBJECTIVE: To determine the effect of an aerobic conditioning program on fitness, respiratory physiology, and resting lung function in patients with mild asthma. DESIGN: Prospective cohort study. SETTING: Outpatient rehabilitation facility. METHODS: Five patients with mild intermittent asthma and five normal control subjects completed a 10-week aerobic conditioning program. Pulmonary function studies and noninvasive cardiopulmonary exercise tests were performed before and after the conditioning program. RESULTS: After aerobic conditioning, there were significant gains in maximum oxygen consumption (VO(2)max; 22.73 mL/kg/min vs 25.29 mL/kg/min, p = 0.01, asthma; 22.94 mL/kg/min vs 27.85 mL/kg/min, p = 0.03, control) and anaerobic threshold (0.99 L/min vs 1.09 L/min, p = 0.03, asthma; 0.89 L/min vs 1.13 L/min, p = 0.01, control) in both groups. Although FEV(1) was unchanged, the maximum voluntary ventilation (MVV) improved in the asthma group (96.0 L/min vs 108.2 L/min, p = 0.08, asthma; 134.0 L/min vs 131.2 L/min, p = 0.35, control). During exercise, minute ventilation (VE) for each level of work was decreased in the asthma group after conditioning, while little change occurred in the control group (68. 48 L/min vs 51.70 L/min at initial VO(2)max, p = 0. 02, asthma; 65.82 L/min vs 63.12 L/min at initial VO(2)max, p = 0.60, control). A significant decrease in the ventilatory equivalent (VE/oxygen consumption, 40.8 vs 30.4 at VO(2)max, p = 0.02, asthma; 37.2 vs 35.8 4 at VO(2)max, p = 0.02, control) and the dyspnea index (VE/MVV) at submaximal (0.44 vs 0.38, p = 0.05, asthma; 0.32 vs 0.38, p < 0.01, control) and maximal exercise (0.72 vs 0.63, p = 0.03, asthma; 0.49 vs 0.62, p = 0.02, control) occurred in the asthma group. CONCLUSIONS: Exercise rehabilitation improves aerobic fitness in both asthmatic and nonasthmatic participants of a 10-week aerobic fitness program. Additional benefits of improved ventilatory capacity and decreased hyperpnea of exercise occurred in patients with mild asthma.

Peripheral blood manifestations of T(H)2 lymphocyte activation in stable atopic asthma and during exercise-induced bronchospasm.

BACKGROUND: Recently, TH2 lymphocyte activation has been shown to play a key role in initiating and propagating the inflammatory response in asthmatic airways. This is manifest through increased numbers of "activated" CD25-(IL-2R)-bearing T-helper cells and can be seen through the IL-5 driven recruitment of eosinophils and IL-4-mediated B-cell expression of CD23 (low affinity IgE receptor) and ultimately IgE production. OBJECTIVE: To gain a better understanding of the role of immune cells in asthma by describing the peripheral blood immune cell phenotypes in mild atopic asthma. METHODS: We enrolled 13 patients with mild atopic asthma and a group of seven nonatopic, nonasthmatic controls. Objective measures of lung function were obtained. The peripheral blood was analyzed by flow cytometry for specific cellular markers at rest and during the development of exercise induced bronchospasm. RESULTS: At rest the number of CD23-bearing B cells (169/mL versus 117/mL; P = .05) and the number of CD25-bearing T cells (355/mL versus 237/mL; P = .03) were increased in the asthma group. There was a linear relationship between these two lymphocyte subsets and the maximum voluntary ventilation at rest (r = 0.56, P = .01 and r = 0.57, P = .01). With the development of exercise-induced bronchospasm there was a significantly greater increase in CD23-positive B cells (96.7/mL versus 59.7/mL; P = .05) and CD25-positive T cells (111.8/mL versus 45.1; P = .01) in the asthma group. CONCLUSIONS: These data indicate that TH2 lymphocyte activation is manifested by increased numbers of CD23-bearing B cells and CD25-bearing T cells in the peripheral blood of patients with stable mild atopic asthma. Further, these immune cell subsets correlate with markers of resting lung function and increase in the peripheral blood early after the development of exercise-induced bronchospasm.