Comparing the harmful effects of nontuberculous mycobacteria and Gram negative bacteria on lung function in patients with cystic fibrosis

BACKGROUND: To better understand the relative effects of infection with nontuberculous mycobacteria and Gram negative bacteria on lung function decline in cystic fibrosis, we assessed the impact of each infection in a Danish setting. METHODS: Longitudinal registry study of 432 patients with cystic fibrosis contributing 53,771 lung function measures between 1974 and 2014. We used a mixed effects model with longitudinally structured correlation, while adjusting for clinically important covariates. RESULTS: Infections with a significant impact on rate of decline in %FEV1 were Mycobacterium abscessus complex with -2.22% points per year (95% CI -3.21 to -1.23), Burkholderia cepacia complex -1.95% (95% CI -2.51 to -1.39), Achromobacterxylosoxidans -1.55% (95% CI -2.21 to -0.90), and Pseudomonas aeruginosa -0.95% (95% CI -1.24 to -0.66). Clearing M. abscessus complex was associated with a change to a slower decline, similar in magnitude to the pre-infection slope. CONCLUSIONS: In a national population we have demonstrated the impact on lung function of each chronic CF pathogen. M. abscessus complex was associated with the worst impact on lung function. Eradication of M. abscessus complex may significantly improve lung function

Chronic infection with Achromobacter xylosoxidans in cystic fibrosis patients; a retrospective case control study

AbstractBackgroundIn cystic fibrosis (CF), chronic infection of the airways with Achromobacter xylosoxidans have become more frequent. The pathogenic role of this is yet unclear.MethodsA retrospective case-control study of all patients chronically infected with A. xylosoxidans for at least 3 years. 15 patients (6 males) with chronic A. xylosoxidans infection were matched by age, FEV1 and body mass index z-score to 15 controls (7 males) at the time of establishment of chronic infection. Clinical parameters of the groups were compared from the time of establishment of chronic infection until spring 2006, giving a follow-up time of 3–11 years. Chest X-rays taken 3 years prior to establishment of chronic infection and after 3 years of chronic infection were compared using a modified Brasfield score. Finally, strains from individual patients were analysed using PFGE to investigate possible cross-infection.ResultsThe median slope of decline of FEV1 in the case group changed from +3.1% to −0.5% predicted/year (p<0.002). In the control group, median slope of decline in FEV1 changed from +1.5% to −0.4% predicted/year (n.s.). Median slope of decline in FVC in the case group changed from +3.5% to −0.5% predicted/year (p<0.002). In the control group, median slope of decline in FVC changed from +1.7% to +0.4% predicted/year (n.s.). No significant difference in the slopes of decline of FEV1 or FVC was found between the case group and the control group at either time. Change in BMI z-score was calculated for each group before and during chronic infection. No difference was found between the groups at any time or within a group. Specific antibodies against A. xylosoxidans were measured in patients with chronic infection. Patients with rapidly increasing antibody levels showed significantly faster deterioration in FEV1 (p<0.05) and FVC (p<0.02).Chest X-ray scores increased in 6 of 10 chronically infected patients and in 3 of 10 controls (n.s.).Eight patients harboured a common A. xylosoxidans strain, indicating either cross-infection or a common source.ConclusionA. xylosoxidans may lead to a decline in lung function in a subgroup of chronically infected CF patients characterised by a rapid increase in specific precipitating antibodies. Cross-infection may possibly occur