Published ahead of print on September 7, 2006, doi:10.1164/rccm.200603-423OC Am. J. Respir. Crit. Care Med., Volume 174, Number 11, December 2006, 1211-1220 A more recent version of this article appeared on December 1, 2006
Submitted on March 24, 2006 Effect of Allergic Broncho-pulmonary Aspergillosis on Lung Function in Children with Cystic FibrosisRichard Kraemer1*,1 Department of Paediatrics, University of Berne, Berne, BE, Switzerland, 2 Department of Psychiatry, University of Berne, Berne, BE, Switzerland, 3 Division of Human Genetics, University of Berne, Berne, BE, Switzerland, 4 Swiss Institute of Allergy and Asthma Research, Davos, GR, Switzerland * To whom correspondence should be addressed. E-mail: richard.kraemer{at}insel.ch.
Rationale. The relationship between sensitization to A. fumigatus (Af) and progression of pulmonary function is not yet established in cystic fibrosis (CF). Objectives. We aimed to evaluate onset of Af-sensitization and development of allergic broncho-pulmonary aspergillosis (ABPA), as well as to determine the physiological factors of lung function influencing these mechanisms in CF. Methods. Serial annual lung function tests performed in 122 CF-children (62 males; 60 females; age: 6-18 y), provided data pertaining to functional residual capacity (FRCpleth), lung clearance index (LCI), volume of trapped gas (VTG), effective specific airway resistance (sReff), and forced expiratory indices (FEV1, FEF50). Specific IgE to recombinant Af allergens rAspf1 and rAspf3, served as marker for sensitization, and to rAspf4 and rAspf6 as indication for a serological ABPA, clinically diagnosed (Nelson criteria). By linear mixed-effect model analysis 5 patient groups, (i) not sensitized and free from P. aeruginosa (PA), (ii) intermittently PA-colonized, (iii) chronically PA-infected, (iv) sensitized, and (v) ABPA, were retrospectively evaluated. Measurements and Main Results. Af sensitization was best reflected by increased rAspf1+3-specific IgE levels, whereas in most patients sensitization was preceded by PA infection. ABPA patients demonstrated the most severe progression in all lung function parameters, and FEF50, VTG and sReff were the best predictor (p<0.0001). However, regarding distinction between sensitization to Af and development of ABPA in the course of CF, chronic PA infection has to be taken into account. Conclusions. Airway narrowing, gas trapping and small airway disease are the major targets for functional derangement in ABPA. Key words: Cystic fibrosis, A. fumigatus sensitization, allergic broncho-pulmonary aspergillosis, lung function, P. aeruginosa infection
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