Gunnar Bylin

Repeated exposure to an ambient level of NO2 enhances asthmatic response to a nonsymptomatic allergen dose

We investigated the effects of NO2 and allergen on lung function in a repeated exposure model. For 4 subsequent days, 16 subjects with mild asthma and allergy to birch or grass pollen were exposed at rest to either purified air or 500 microg x m(-3) NO2 for 30 min in an exposure chamber. Four hours later, an individually determined nonsymptomatic allergen dose was inhaled. Lung function (forced expiratory volume in one second (FEV1)) was measured by a portable spirometer at early phase (EP) 15 min after allergen and at late phase (LP) 3-10 h after allergen. Subjective symptoms and medication were followed by diary cards. Asthmatic response was significantly increased after repeated exposure to NO2 and allergen compared to air and allergen. The 4-day mean fall in FEV1 after NO2 was at EP -25% versus -0.4% for air (p=0.02) and at LP -4.4% versus -1.9% for air (p=0.01, ANOVA). An increase in EP response was seen already after a single NO2 exposure (p=0.03). There was a tendency (p=0.07) towards increased night-time symptoms of asthma after NO2 plus allergen. Although the effects were small, the results indicate that a repeated short exposure to an ambient level of NO2 enhances the airway response to a nonsymptomatic allergen dose.

Deposition of inhaled particles in the mouth and throat of asthmatic subjects

We previously studied the deposition of inhaled particles in the mouth and throat of asthmatic patients, and found large, reproducible differences among subjects. In the present study, we examined whether anatomical and/or functional differences in the pharynx and larynx could underlie this interindividual variation. Deposition in the mouth and throat, and in the lung was estimated in 16 asthmatic subjects after inhalation of 3.6 microns (aerodynamic diameter) monodisperse Teflon particles labelled with 111In. The particles were inhaled at a flow rate of 0.5 l.s-1 with maximally deep breaths. Radioactivity was measured by external scanning over head and neck, lungs and stomach, immediately after the inhalation. Radioactivity in the lungs was also measured 24 h later. A measure of the total amount of particles deposited in the mouth and throat was obtained from the added activities in mouthwash, head and neck, and stomach, immediately after the inhalation of the test particles. Pharynx and larynx function was examined by fibreoptic laryngoscopy performed during a corresponding inhalation procedure. Deposition in the mouth and throat varied widely among the subjects, ranging 9-76% (median 12%). We found two subpopulations, 13 subjects in the range 9-34%, and 3 subjects with > 70% deposition. Deviations in pharyngeal configuration during inhalation were significantly related to high mouth and throat deposition, whereas functional differences in the larynx were not. Our study shows that mouth and throat deposition may be extremely high in some asthmatics, and that pharyngeal configuration affects deposition of particles in the mouth and throat.

Immediate and delayed effects of nitrogen dioxide exposure at an ambient level on bronchial responsiveness to histamine in subjects with asthma

The time-kinetics of NO2 induced effects on bronchial responsiveness are poorly known as most observations have been made shortly after exposure. The aim of this study was to measure nonspecific bronchial responsiveness, lung function and inflammatory markers at different times after NO2 exposure in asthmatics. Nineteen subjects with mild asthma were exposed to either purified air or 488 micrograms.m-3 (0.26 ppm) NO2 for 30 min during intermittent exercise. Airway responsiveness to histamine, specific airway resistance (sRaw) and thoracic gas volume (TGV) were measured 30 min, 5 h, 27 h and 7 days after exposure. Peripheral blood inflammatory mediators and the expression of an adhesion molecule, (Mac1) on granulocytes, were analysed 30 min and 27 h after exposure. Bronchial responsiveness to histamine was significantly increased 5 h after NO2 exposure when compared to air (median provocative dose of histamine required to cause 100% increase of sRaw ((PDsRaw,100%) 110 micrograms after NO2 exposure vs 203 micrograms on air). There was a tendency for an increase after 30 min, which was nonsignificant (median PDsRaw,100% 100 vs 153 micrograms). NO2 exposure did not affect sRaw, but TGV was significantly reduced after exposure. We found an increased expression of Mac-1 on granulocytes 30 min after NO2 exposure when compared to pre-exposure values. No effect was seen on tryptase, eosinophil cationic protein (ECP), or myeloperoxidase (MPO). These results suggest that exposure to an ambient level of NO2 causes a delayed effect on bronchial responsiveness in asthmatics. The increased expression of an adhesion molecule in peripheral blood may indicate a NO2-induced priming of human granulocytes.

Peripheral neutrophils after allergic asthmatic reactions

The response of peripheral neutrophils was studied in 16 patients with allergic asthma after challenge with birch/grass pollen allergen, in order to identify inflammatory markers associated with only the early asthmatic reaction and those associated with both early and late asthmatic reactions. The allergen challenge proceeded until the patients had an early asthmatic reaction with 100% increase in specific airway resistance. Bronchoconstriction after allergen challenge was monitored hourly over 9 h and finally after 18 h, by measurement of the forced expiratory volume in 1 s. Seven patients had a late reaction, defined as a decrease in forced expiratory volume in 1 s of more than 15%. Blood samples were taken before and 18 h after challenge. After allergen challenge (18 h) the blood concentration of neutrophils in patients with a late asthmatic reaction was 1.4 times higher than before challenge and there was a tendency for increased Fcγ receptor-mediated chemiluminescence. Lewis X-antigen (CD 15), which is associated with endothelial adhesion and extravasation, significantly decreased at the same time. Neutrophils were incubated with the tetrapeptide arginine-glycine-aspartate-serine before and 18 h after allergen challenge. Both patient groups showed an increased Fcγ receptor-mediated chemiluminescence and a decreased Fcγ receptor membrane expression following allergen challenge, suggesting a preactivation. In conclusion, patients with a dual asthmatic reaction show a sustained primed inflammatory response and primed neutrophils compared with patients with only an early reaction when measured after the decline of clinical symptoms provoked by allergen challenge.

Clearance in Small Ciliated Airways in Allergic Asthmatics after Bronchial Allergen Provocation

Background: Asthma tends to affect mucociliary clearance, as assessed from measurements in large airways. However, there is no knowledge about clearance in the smallest airways of the tracheobronchial region in acute exacerbation of asthma. Objective: The aim of the study was to investigate clearance from the bronchiolar region in patients with allergic asthma in a situation resembling a mild acute exacerbation of the disease. We also aimed to compare clearance data with corresponding data found for healthy subjects and asthmatics on therapy. Methods: Tracheobronchial clearance was studied twice in 9 patients with mild asthma of the allergic type after inhalation of 6 μm (aerodynamic diameter) monodisperse Teflon particles labelled with 111In. At one exposure, inhalation was performed 4 h after bronchial provocation with an allergen the patients were allergic to. The second exposure was a control measurement. The particles were inhaled at an extremely slow flow, 0.05 liter/s, which gives deposition mainly in the small ciliated airways (bronchioles). Lung retention was measured at 0, 24, 48 and 72 h. Results: All patients demonstrated an early asthmatic reaction of varying degree after bronchial provocation. There was significant clearance of radioaerosol in each 24-hour period for both exposures, with the possible exception of the period between 24 and 48 h for the provocation exposure, with similar fractions of retained particles at all points of time. The retained fractions were significantly larger compared to a group of healthy subjects and asthmatics on regular treatment with anti-inflammatory drugs. Conclusions: Our results indicate that in allergic asthmatics a bronchial allergen provocation with an early asthmatic reaction does not significantly influence overall clearance from the bronchiolar region. However, in the present group of patients, retention in small ciliated airways was significantly higher compared to healthy subjects and asthmatics on regular treatment.

An Unusual Cause of a Persistent Pulmonary Infiltrate and Weight Loss

Accessible online at: http://BioMedNet.com/karger A 71-year-old smoker was admitted for investigation of suspected lung cancer. He had had a history of coughing for several weeks, the chest roentgenogram showed a vague infiltrate in the lingula and he was put on a course of oral antibiotics. Over a period of 2 months the patient lost 10 kg and the infiltrate did not resolve. Before bronchoscopy a CT scan (fig. 1) was performed, which confirmed the chest roentgenogram findings but did not reveal a tumor. Bronchoscopy surprisingly revealed a grain of maize at the entrance of each lingular segment (fig. 2). Both foreign bodies could be passed with the closed forceps and removed by drawing back the opened forceps with the help of a strong cough from the patient. The lingular infiltrate disappeared subsequently and while treating a painful buccal ulcer, a substantial increase in weight was noticed. In this case the combination of weight loss and a persistent pulmonary infiltrate was not the result of a bronchial tumor, as we expected, but due to an ill-fitting dental prosthesis, which caused the painful buccal ulcer and possibly also favoured aspiration. Our patient, who was very fond of maize salad, could not remember a coughing fit while eating in the past few days or weeks. Even without a typical history, aspiration should always be considered as a possible cause of a pulmonary infiltrate, especially in elderly patients. Figure 3 shows the moderately inflamed entrance to the lingular segments after the procedure. 2