Figures
- FIGURE 1
Microbial features significantly associated with either a) clinical (nontuberculous mycobacteria (NTM) pulmonary disease) or b–e) microbiological (transient versus persistent infection) NTM outcomes. Operational taxonomic units (OTUs) are labelled at genus level, and boxplots show the median and interquartile range. All p-values<0.05, Wilcoxon rank-sum testing.
- FIGURE 2
Differences in bacterial community interactions between cohorts with and without nontuberculous mycobacteria (NTM) pulmonary disease. Heat maps of autoregressive integrated moving averages (ARIMA) model show mean pairwise effect sizes of interacting operational taxonomic units (OTUs) in subjects a) with and c) without NTM pulmonary disease. In the heat map, OTUs on the horizontal axis affect the OTUs on the vertical axis. The heat map colours indicate the magnitude and direction of the OTU interactions (positive interactions in blue, negative interactions in red). In the network graphs of subjects b) with and d) without NTM pulmonary disease, each vertex represents the genus-level grouping of all OTUs included in that ARIMA model. Vertices are coloured by cluster, and are sized by OTU relative abundance. The edges are coloured according to their ARIMA correlation coefficients as shown on the heat maps. Arrows indicate the directionality of the network relationships, i.e. the predicting genus points toward the predicted genus. Due to the asymmetric nature of the ARIMA correlation matrix and the genus-level grouping of OTUs, multiple edges between each pair of vertices are possible.
- FIGURE 3
Differences in bacterial community interactions between cohorts with persistent compared to transient nontuberculous mycobacteria (NTM) infection. Heat maps of autoregressive integrated moving averages (ARIMA) model show mean pairwise effect sizes of interacting operational taxonomic units (OTUs) in subjects with a) persistent and c) transient NTM infection. In the heat map, OTUs on the horizontal axis affect the OTUs on the vertical axis. The heat map colours indicate the magnitude and direction of the OTU interactions (positive interactions in blue, negative interactions in red). In the network graphs of subjects with b) persistent and d) transient NTM infection, each vertex represents the genus-level grouping of all OTUs included in that ARIMA model. Vertices are coloured by cluster, and are sized by OTU relative abundance. The edges are coloured according to their ARIMA correlation coefficients as shown on the heat maps. Arrows indicate the directionality of the network relationships, i.e. the predicting genus points toward the predicted genus.
Tables
- TABLE 1
Sputum sample characteristics
No NTM pulmonary disease NTM pulmonary disease p-value Subjects 16 8 Total sputum samples (mean per subject, range) 129 (8.1, 3–19) 59 (7.4, 3–14) 0.73 (unpaired t-test) Sample clinical state# Baseline 30 (23.3) 22 (37.3) 0.06 (Chi-squared test) Exacerbation 37 (28.7) 18 (30.5) Treatment 42 (32.6) 9 (15.3) Recovery 20 (15.5) 10 (16.9) Data are presented as n or n (%), unless otherwise stated. NTM: nontuberculous mycobacteria. #: defined in the supplementary methods.
- TABLE 2
Subject demographics and clinical characteristics
No NTM pulmonary disease NTM pulmonary disease p-value Subjects 16 8 Age years# 27.3 (21.9–37.7) 25.8 (19.7–32.7) 0.83 Male 9 (56.2) 2 (25) 0.15 CF genotype F508del homozygous 4 (25) 3 (37.5) 0.49 F508del heterozygous 11 (68.8) 4 (50) Other 1 (6.3) 1 (12.5) 0.59 NTM species M. avium complex 9 (56.2) 6 (75) 0.81 M. abscessus complex 4 (25) 2 (25) Other 3 (18.6) 0 (0) 0.42 AFB smear positive# 2 (12.5) 2 (25) 0.44 ppFEV1# 55 (37–69) 68 (43–80) 0.41 Disease aggressiveness¶,+ Mild 9 (56.2) 3 (37.5) Moderate 4 (25) 3 (37.5) 0.47 Severe 3 (18.6) 2 (25) 0.59 BMI#,+ Acceptable 4 (40) 1 (33.3) At risk 2 (20) 1 (33.3) 0.75 Nutritional failure 4 (40) 1 (33.3) 1 CF respiratory cultures# P. aeruginosa 9 (56.2) 6 (75) 0.55 S. aureus 14 (87.5) 3 (37.5) 0.01 S. maltophilia 3 (18.6) 0 (0) 0.38 Achromobacter spp. 2 (12.5) 1 (12.5) 1 Burkholderia spp. 0 (0) 0 (0) Aspergillus spp. 5 (31.3) 2 (25) 1 CF respiratory cultures, ≥1 positive¶ P. aeruginosa 10 (62.5) 6 (75) 0.57 S. aureus 16 (100) 6 (75) 0.07 S. maltophilia 3 (18.6) 1 (12.5) 1 Achromobacter spp. 3 (18.6) 1 (12.5) 1 Burkholderia spp. 1 (6.3) 0 (0) 1 Aspergillus spp. 6 (37.5) 6 (75) 0.13 Diagnosis of CF-related diabetes¶ 5 (31.3) 4 (50) 0.33 Pulmonary exacerbations¶,+ 2 (0.75–5) 2 (1.75–3.75) 0.88 Use of chronic azithromycin¶ 9 (56.2) 5 (62.5) 1 Use of chronic inhaled antibiotics¶ 10 (62.5) 6 (75) 0.57 Use of inhaled steroids¶ 10 (62.5) 8 (100) 0.04 Data are presented as n, median (interquartile range) or n (%), unless otherwise stated. NTM: nontuberculous mycobacteria; CF: cystic fibrosis; M. avium: Mycobacterium avium; M. abscessus: Mycobacterium abscessus; AFB: acid-fast bacilli; ppFEV1: percentage predicted forced expiratory volume in 1 s; BMI: body mass index; P. aeruginosa: Pseudomonas aeruginosa; S. aureus: Staphylococcus aureus; S. maltophilia: Stenotrophomonas maltophilia. #: at incident NTM infection; ¶: within 1 year prior to incident NTM infection; +: details in supplementary methods.
- TABLE 3
Autoregressive integrated moving averages (ARIMA) correlation coefficients of clinical and microbiological nontuberculous mycobacteria (NTM) outcomes with all operational taxonomic units (OTUs) included in final ARIMA model. The colours indicate the magnitude and direction of the effect of the outcomes on the OTUs, with the maximum negative effect (−1.79) in red, the maximum positive effect (1.14) in blue, and no effect in white.
Supplementary Material
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Supplementary figures and tables 00578-2020.supplementary_figs_tabs
Supplementary methods 00578-2020.supplementary_methods
