Bronchial hyperreactivity related to 4 commonly used inhalation drugs in Belgian cystic fibrosis

Background: Short-term tolerability of inhaled hypertonic saline (HS 6%),rhDNase, tobramycin and colistin in CF has been investigated before.Bronchial hyperreactivity (BHR) is reported in up to one third of the CFpatients. BHR due to chronic inhalation of these drugs is poorly documented.Aims: To examine the prevalence of BHR related to chronic inhalation ofpreviously described drugs leading to mandatory termination of therapy.To determine risk factors for appearance of BHR, such as adulthood, durationof treatment, characteristics of specific drugs and presence of atopic disease.Methods: All CF patients’ files of the University Hospital Brussels werescreened from January 2002 till October 2012 related to the use of inhaledHS 6%, rhDNase, tobramycin and colistin after bronchodilation. Start andend date of inhalation treatment were registered and if applicable, reason forending inhalation.Results: A total of 163 (91M) patients were included with a median age of17 years (0–61; n <18y ¼ 84) and median number of inhaled drugs pp. perday was 2 (range 0–4).BHR occurred in 29 patients (17.8%), mostly in adults (26.6% vs. 9.5%<18y; P <.05) and after a median of 1086.5 days (0–3740 days). Asignificant correlation was found between number of inhaled drugs pp. perday and the occurrence of BHR (t ¼ .25; P <.001).The occurrence of BHR was significant after inhalation of HS 6% (19.6%(P < .001)) and antibiotics (tobramycin 16.2% (P <.001); colistin 10.1%(P < .05)), but not after inhalation of rhDNase (1.4%; P ¼.61).Atopic constitution, documented by positive Skin Prick Test foraeroallergens (66.7% vs. 51.9%) and elevated IgE levels (44.8% vs33.6%), was not significantly higher in CF patients with BHR compared toCF patients without BHR (Pearson Chi-square .312 and .256 respectively).Conclusions: BHR is seen more often in adults and after chronic inhalation,despite preceded preventive bronchodilation. Furthermore, it depends on thetype of drug and increases with the number of taken aerosols per day. Thesefindings may be suggestive for a cumulative effect of inhalation therapy onBHR. In addition, atopic disease does not seem to influence the presence ofBHR.