Nerve growth factor in serum and lymphocyte culture in pigeon fanciers' acute hypersensitivity pneumonitis.

BACKGROUND: Nerve growth factor (NGF) is a neurotrophic cytokine with immunomodulatory activity. NGF contributes to neurogenic inflammation and has been described in asthma and idiopathic pulmonary fibrosis. OBJECTIVES: To identify and quantify NGF in serum and peripheral blood lymphocyte cultures from pigeon fanciers, and to investigate an association with the immune response to inhaled avian antigens, and with symptoms of acute hypersensitivity pneumonitis (HP). METHODS: NGF was quantified and compared with serum IgG antibody against inhaled avian antigens, with serum C-reactive protein (CRP), and with KL-6, a marker of lung interstitial inflammation. These were measured using enzyme-linked immunoassay. Levels were compared with symptom history in 55 pigeon fanciers (26 subjects with acute HP but symptom-free at the time of testing) and 15 subjects with no avian exposure. RESULTS: Pigeon fanciers had higher-than-normal serum IgG antibody, CRP, and KL-6 levels (p < 0.01 each). These measures were unrelated to HP symptom category; instead, in all pigeon fanciers, the concentrations of CRP and KL-6 correlated with each other and with the antibody titers (p < 0.01 each). Serum NGF levels were normal; however, NGF production by mitogen-activated lymphocytes was higher than normal, and correlated with IgG antibody titer (p < 0.05) and with serum CRP (p < 0.05). CONCLUSIONS: Serum NGF was normal in pigeon fanciers; however, their blood lymphocytes ex vivo synthesized increased NGF in concentrations that correlated with the titer of serum IgG antibody to inhaled avian antigens. These also correlated with CRP and KL-6 levels, suggesting that antigen exposure in seropositive subjects is associated with subclinical inflammation involving coordinated synthesis of neurotrophin and immune mediators.

Effects of smoking cessation on lung function and airway inflammation in smokers with asthma.

RATIONALE: Active smoking in asthma is associated with worsening of symptoms, accelerated decline in lung function, and impaired response to corticosteroids. OBJECTIVES: To examine the short-term effects of smoking cessation on lung function, airway inflammation, and corticosteroid responsiveness in smokers with asthma. METHODS AND MEASUREMENTS: Smokers with asthma were given the option to quit or continue smoking. Both groups underwent spirometry and induced sputum at baseline and at 1, 3, and 6 wk. Cutaneous vasoconstrictor response to topical beclometasone, airway response to oral prednisolone, and sensitivity of peripheral blood lymphocytes to corticosteroids were measured before smoking cessation and at 6 wk. MAIN RESULTS: Of 32 subjects recruited, 11 opted to continue smoking (smoking control group). Of 21 subjects who opted for smoking cessation, 10 quit smoking for 6 wk (quit group). In the comparison of quitters with smokers at 6 wk, the mean (confidence interval [CI]) difference in FEV(1) was 407 ml (21, 793), p = 0.040, and the proportion of sputum neutrophils was reduced by 29 (51, 8), p = 0.039. Total cutaneous vasoconstrictor response score to topical beclometasone improved after smoking cessation with a mean (CI) difference of 3.56 (0.84, 6.28), p = 0.042, between quitters and smokers. There was no change in airway corticosteroid responses after smoking cessation. CONCLUSIONS: By 6 wk after smoking cessation, subjects who quit smoking had achieved considerable improvement in lung function and a fall in sputum neutrophil count compared with subjects who continued to smoke. These findings highlight the importance of smoking cessation in asthma.

Short and long-term effects of cigarette smoking independently influence exhaled nitric oxide concentration in asthma.

BACKGROUND: The fractional concentration of nitric oxide in exhaled breath (FeNO) is elevated in asthma. FeNO measurement has been proposed as a noninvasive index of disease activity. Cigarette smoking suppresses FeNO, which limits its use in smokers. OBJECTIVE: To identify and model short-term and long-term influences of cigarette smoking on FeNO. METHODS: The smoking history, FeNO, and fractional concentration of carbon monoxide in exhaled breath (FeCO) were measured in 53 subjects with asthma and 51 control subjects. A mathematical model of the short-term and long-term effects of cigarette smoking on FeNO was derived. RESULTS: Subjects with asthma had higher FeNO than controls ( P < .001). Smokers had increased FeCO ( P < .001). The short-term effect (hours since last cigarette) was associated with increased FeNO ( P < .01) and decreased FeCO ( P < .05). The long-term effect (years smoked) was associated with decreasing FeNO only in the subjects with asthma ( r = -0.62; P = .005). These short-term and long-term effects were independent and were combined in a model predicting FeNO, predicted log 10 FeNO = 1.23 - 0.58 e -0.34t - 0.00000103 x (lifetime cigarettes), where t = hours since the last cigarette. This gave a convincing prediction of FeNO ( r = 0.83; P < .0001). CONCLUSION: Short-term and long-term effects of smoking influenced the measurement of FeNO. We defined a model that describes these effects. The use of this formula may improve the value of FeNO measurements in smokers with asthma.