Bronchial Challenge Tests in Patients with Asthma Sensitized to Cats

Abstract

Our aim was to compare bronchial responses to major cat allergen (Fel d 1) in individuals with intermittent asthma sensitized to cats (19 subjects) according to the droplet particle size. We used three nebulizers, which delivered particles with mass median aerodynamic diameters of 1.4, 4.8, and 10.3 microm. A dosimeter nebulizer was used. The cat allergen was diluted to obtain the same amount of Fel d 1 per puff with each nebulizer. Each patient underwent three methacholine bronchial challenge tests (BCT), each followed 24 hours later by a cat allergen BCT, each performed with a different nebulizer (randomly selected each time, with patient and tester always blinded). Subjects did not differ for methacholine responsiveness, FEV1, mean forced expiratory flow during the middle half of the FVC (FEF25-75), PEF, or dyspnea (Borg scale) before any of the three cat BCTs. Cat allergen PD20 was 271 ng of Fel d 1 with the 1.4 microm nebulizer, 46 ng with the 4.8 microm nebulizer, and 13.5 ng with the 10.3 microm nebulizer (p = 0.00001). Inhalation of small particles (1.4 microm) resulted in significantly lower FEF25-75 24 hours after provocation than large particles did. In conclusion, immediate bronchial response appears to be localized in large airways, and the use of large particles is more appropriate for cat allergen BCTs.

New data analysis in a population study raises the hypothesis that particle size contributes to the pro-asthmatic potential of small pet animal allergens

“…Subjects sensitized to small particles were more likely to have higher airway responsiveness compared with subjects sensitized only to large particles. That contradicts results of previous studies where larger aerosols of adenosine monophosphate ( 41 ), methacholine ( 14 ), cat allergen ( 42 ), and mite allergen ( 43 ) gave more immediate responses than smaller particles. The same quantity could be delivered in both large and small airways with the nebulizer, but the concentration relative to the area of deposition in the larger airways would be higher as deposition of the same dose in the small airways could be insufficient to achieve similar airway bronchoconstriction due to the larger area of the small airways.…”

“…To our knowledge, few studies ( 14 , 41 – 43 ) examined the effects of IgE sensitization with regard to particle size on the airways responsiveness, lung function, and markers of systemic inflammation during bronchial challenge tests. Differential immediate and late allergic responses were reported in relation to particle size with small allergen particles leading to significantly lower FEF 25–75 at 24 h after provocation compared with large particles ( 42 ). Our study demonstrated a differential response to smaller allergen particles (for example cat and dog) leading to an increase of F E NO 50 , mainly explained by an increase in airway concentration of NO but no effect on alveolar contribution to NO.…”

An update on molecular cat allergens: Fel d 1 and what else? Chapter 1: Fel d 1, the major cat allergen

“…The immediate bronchial response to Fel d 1 appears to be located in the proximal airways. The concentration of Fel d 1 required to induce a positive bronchial response in subjects with intermittent asthma was 20 times less when the allergen was carried by large particles (10.3 μm) than when Fel d 1 was carried by small particles (1.4 μm) [ 36 ]. However, a more recent article suggests that exposure under natural conditions to cat allergens (and not just to Fel d 1) induces a more peripheral airway obstruction [ 37 ].…”

Low‐dose endotoxin in allergic asthmatics: effect on bronchial and inflammatory response to cat allergen

“…Indeed, whereas in the Boehlecke study the mass median aerodynamic diameter of endotoxin particles was 4.9 μm, we chose to nebulize particles with a medium mass aerodynamic diameter of 10 μm. Indeed, we have recently demonstrated that the levels of Fel d 1 that induced immediate bronchial response in asthmatic patients were 20 times lower when the allergen was carried by large particles [18]. According to preliminary data on airborne endotoxin measurements with cascade impactor in swineries, we also nebulized endotoxin on large particles.…”