H. F. Kauffman

In order to obtain information about the nature of the local inflammatory process during late asthmatic reactions after house dust mite inhalation, bronchoalveolar lavage (BAL) was performed in 19 asthmatic patients and in 5 control subjects. In 16 of the patients and in all of the control subjects, BAL was performed 6 to 7 h after allergen inhalation. Six of the patients showed early and late asthmatic reactions (LAR), 5 showed early reactions, and 5 showed no reactions. Bronchoalveolar lavage was also performed shortly after the early reaction in 5 patients with documented combined early and late reactions. In the BAL fluid of the patients with LAR, a significant eosinophilia (0.01 less than p less than 0.05) was found compared with that in all other patient groups and with that in the control subjects. This bronchoalveolar eosinophilia was accompanied by elevated eosinophil cationic protein/albumin ratio in the BAL fluid (0.01 less than p less than 0.05). These observations suggest that eosinophils and their mediators might be involved in the development of LAR after allergen inhalation.

Summary Background Studies have been performed suggesting that administration of probiotics may have therapeutic and/or preventive benefits in the development of sensitization and atopic disease, particularly in infants with atopic dermatitis (AD). Objective The purpose of this study was to evaluate the clinical and immunological effects of supplementation of a hydrolysed formula with two probiotic strains of bacteria on symptoms of AD in infancy. Methods We conducted a randomized, double‐blind, placebo‐controlled study. After 4–6 weeks of baseline and double‐blind, placebo‐controlled challenges for diagnosis of cow's milk allergy (CMA), infants less than 5 months old with AD received a hydrolysed whey‐based formula as placebo ( n =17), or supplemented with either Lactobacillus rhamnosus ( n =17) or Lactobacillus GG ( n =16) for 3 months. Before, during and after intervention, the clinical severity of AD was evaluated using SCORing index Atopic Dermatitis (SCORAD). Allergic sensitization was evaluated by measurement of total IgE and a panel of food‐specific IgEs as well as skin prick testing for cow's milk. Inflammatory parameters were blood eosinophils, eosinophil protein X in urine, fecal α‐1‐antitrypsin and production of IL‐4, IL‐5 and IFN‐γ by peripheral blood mononuclear cells after polyclonal stimulation. Results No statistically significant effects of probiotic supplementation on SCORAD, sensitization, inflammatory parameters or cytokine production between groups were found. Only four infants were diagnosed with CMA. Conclusion We found no clinical or immunological effect of the probiotic bacteria used in infants with AD. Our results indicate that oral supplementation with these probiotic bacterial strains will not have a significant impact on the symptoms of infantile AD.

Previous studies have suggested that endogenous protease inhibitors may participate in the mucosal host defense. Antileukoprotease (ALP) is an important protease inhibitor found on various mucosal surfaces, including those of the respiratory and genital tracts. This study reports on the antimicrobial activity of recombinant (r) ALP toward the human fungal pathogens Aspergillus fumigatus and Candida albicans. rALP expressed pronounced fungicidal activity toward metabolically active A. fumigatus conidia and C. albicans yeast cells; however, metabolically quiescent A. fumigatus conidia were totally resistant. In contrast with the protease inhibitory activity of rALP, the fungicidal activity was localized primarily in the NH2-terminal domain. On a molar base, the fungicidal activity of rALP was comparable with that of human defensins and lysozyme. In addition, rALP caused inhibition of C. albicans yeast cell growth. By exhibiting antifungal activity, ALP may play an important role in the innate mucosal defense against human pathogenic fungi.

Fungus-induced obstructive airway disease in atopic individuals can be differentiated into two categories: first, uncomplicated asthmatic reactions due to high but transient exposure to fungal spores (fungal asthma), resulting in a TH2-type response with immunoglobulin E-mediated reactions and eosinophilic inflammation; and second, a more complex asthmatic reaction due to colonization of the mucus-epithelial surface by virulent protease-producing fungi. The latter condition stimulates as exaggerated immunological response including all subclasses of antibodies directed against the microorganism and an intense eosinophilic infiltrate of the airways. The authors propose that the exaggerated inflammatory response in allergic bronchopulmonary fungosis damages epithelial cells and underlying tissue cells, resulting in inefficient elimination of the microorganisms and damage to matrix proteins of the lung tissue by proteases released by both the fungi and degranulating eosinophils. The positive effects of corticosteroids in the treatment of allergic bronchopulmonary aspergillosis probably results from the dampening of the inflammatory response and an increase of the efficiency of killing the fungi. Sensitization to fungi is high in childhood and declines rapidly with age, suggesting that younger children may be less proficient in clearing fungi from the airways. We propose that insufficient treatment of fungal asthma may result in damage to the bronchial mucosa and formation of bronchiectasis.

BACKGROUND: Nitric oxide (NO) is involved in inflammation and host defence of the lung. It has been found in increased concentrations in the airways in asthmatic subjects but its levels in patients with chronic obstructive pulmonary disease (COPD) have not been investigated. A study was undertaken to determine whether markers of NO metabolism (NO in exhaled air, iNOS expression in sputum cells, and nitrite + nitrate (NO2-/NO3-) in sputum supernatant) are increased in subjects with COPD, and whether they correlate with inflammatory indices in induced sputum. The associations of these markers with smoking were also assessed. METHODS: Sixteen subjects with COPD (median age 66 years, median forced expiratory volume in one second (FEV1) 63% predicted, eight current smokers) and 16 healthy subjects (median age 63 years, median FEV1 113% predicted, eight current smokers) participated in the study. NO was measured during tidal breathing and sputum was induced by inhalation of hypertonic saline. RESULTS: No differences were observed between subjects with COPD and healthy controls in exhaled NO excretion rate (median 5.15 and 6.25 nmol/min), sputum macrophage iNOS expression (14% and 12%), and sputum supernatant NO2-/NO3- (46 and 73 microM). NO in exhaled air correlated with the percentage of sputum eosinophils in patients with COPD (rho = 0.65, p = 0.009) but not in healthy individuals. Exhaled NO and supernatant NO2-/NO3- levels were lower in healthy smokers than in healthy non/ex-smokers. CONCLUSIONS: Our findings indicate that NO metabolism is not increased in patients with stable COPD. The close association between exhaled NO levels and sputum eosinophils suggests a role for NO in airway inflammation in COPD. Studies performed during exacerbations may clarify this role.