Chronic Mycobacterium abscessus infection and lung function decline in cystic fibrosis

Abstract

Background: Although nontuberculous mycobacteria (NTM) are recognized pathogens in cystic fibrosis (CF), associations with clinical outcomes remain unclear.

Methods: Microbiological data was obtained from 1216 CF patients over 8years (481+/-55patients/year). Relationships to clinical outcomes were examined in the subset (n=271, 203+/-23 patients/year) with longitudinal data.

Results: Five hundred thirty-six of 4862 (11%) acid-fast bacilli (AFB) cultures grew NTM, with Mycobacterium abscessus (n=298, 55.6%) and Mycobacterium avium complex (n=190, 35.4%) most common. Associated bacterial cultures grew Stenotrophomonas or Aspergillus species more often when NTM were isolated (18.2% vs. 8.4% and 13.9% vs. 7.2%, respectively, p<0.01). After controlling for confounders, patients with chronic M. abscessus infection had greater rates of lung function decline than those with no NTM infection (-2.52 vs. -1.64% predicted FEV(1)/year, p<0.05).

Conclusions: NTM infection is common in CF and associated with particular pathogens. Chronic M. abscessus infection is associated with increased lung function decline.

Fig. 1

Prevalence of NTM species and associated pathogens. A) Relative distribution of NTM species (n=536). M. abs=M. abscessus, M. avi=M. avium complex, and M. gor=M. gordonae. Others included all other NTM, predominantly unidentified species (n=33) but small numbers of M. fortuitum (n=3), M. B) Frequency of culture positivity for various CF pathogens in bacterial/fungal cultures associated with NTM+ or NTM− AFB cultures. P. aer=P. aeruginosa, S. aur=Staphylococcus aureus, S. mal=S. maltophilia, and A. xyl=Achromobacter xylosoxidans. A. fum=Aspergillus fumigatus. *p<0.05 NTM+ vs. NTM− by Chi-squared analysis.

Fig. 2

Age distribution and annual prevalence of NTM infection. Prevalence was calculated form records of 1216 CF patients with at least one microbiological culture obtained from a single university CF center from 2000 to 2007. A) For each year of age, the percentage of patients with at least one AFB culture attempt (squares) was determined, as was the percentage of patients with at least one culture positive for NTM among all patients (triangles) and AFB screened patients (circles). Older patients were more likely to have both AFB culture attempts and NTM isolated from AFB cultures. B) For each calendar year of the study, the percentage of patients with at least one AFB culture attempt (squares) and at least culture positive for NTM among all patients (triangles) and AFB screened patients (circles) was determined. Among all patients, the percentage of AFB cultures and NTM positive cultures increased over time, although the percentage of NTM positive cultures among AFB screened patients remained relatively constant.

Fig. 3

Prevalence of NTM in patients with longitudinal clinical data. The subset of CF patients with at least three AFB culture attempts and at least 3 years of lung function data was examined (n=271). Within this group, the percentage of patients with at least one AFB culture attempt (squares) and at least one positive culture for NTM among all patients (triangles) and those patients with least one AFB culture attempt (circles) was determined. As with the larger group, the percentage of patients with AFB cultures and NTM positive cultures increased over time, although the percentage of patients with AFB culture attempts that were NTM positive was relatively constant.

Fig. 4

Model of changes in FEV1 % predicted over time in chronic NTM infection, adjusted for confounders. Using the data from Table 2, a model of lung function decline over time was generated for groups of patients with no NTM infection (solid line) and chronic M. abscessus infection (dashed line) after adjustment for potential confounders. This model demonstrates the worsening decline in lung function over time in the chronic M. abscessus infection group.