Seasonal fluctuation of lung function in cystic fibrosis:A national register-based study in two northern European populations

Background Many risk factors for lung disease in cystic fibrosis (CF) display a seasonal pattern yet it is unclear whether this is reflected in seasonal fluctuations in lung function. Methods We conducted a longitudinal study using CF registries in Denmark and the UK. 485 individuals with a median of 103 FEV1 measurements per person and 7622 individuals with a median of nine FEV1 measures per person were included from Denmark and the UK respectively. We estimated the effect of seasonality on percent predicted FEV1 trajectories using mixed effects models whilst adjusting for clinically important covariates. Results We found no significant cyclical seasonal variation in lung function in either country. The maximum variation in percent predicted FEV1 around the yearly average was estimated to be 0.1 percentage points (95%CI 0 to 0.21) and 0.14 percentage points (95%CI 0 to 0.29) in Denmark and the UK, respectively. When considering possible step-like changes between the four seasons, we found that lung function was higher in spring compared to winter in the UK (0.34 percentage points, 95%CI 0.1 to 0.59) though the difference was not of clinical significance. Conclusion In both the UK and Denmark there may be small seasonal changes in lung function but this effect is not of clinical importance

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

Comparison of the Outcomes of Individuals With Medically Attended Influenza A and B Virus Infections Enrolled in 2 International Cohort Studies Over a 6-Year Period: 2009-2015.

BACKGROUND: Outcome data from prospective follow-up studies comparing infections with different influenza virus types/subtypes are limited. METHODS: Demographic, clinical characteristics and follow-up outcomes for adults with laboratory-confirmed influenza A(H1N1)pdm09, A(H3N2), or B virus infections were compared in 2 prospective cohorts enrolled globally from 2009 through 2015. Logistic regression was used to compare outcomes among influenza virus type/subtypes. RESULTS: Of 3952 outpatients, 1290 (32.6%) had A(H1N1)pdm09 virus infection, 1857 (47.0%) had A(H3N2), and 805 (20.4%) had influenza B. Of 1398 inpatients, 641 (45.8%) had A(H1N1)pdm09, 532 (38.1%) had A(H3N2), and 225 (16.1%) had influenza B. Outpatients with A(H1N1)pdm09 were younger with fewer comorbidities and were more likely to be hospitalized during the 14-day follow-up (3.3%) than influenza B (2.2%) or A(H3N2) (0.7%; P < .0001). Hospitalized patients with A(H1N1)pdm09 (20.3%) were more likely to be enrolled from intensive care units (ICUs) than those with A(H3N2) (11.3%) or B (9.8%; P < .0001). However, 60-day follow-up of discharged inpatients showed no difference in disease progression (P = .32) or all-cause mortality (P = .30) among influenza types/subtypes. These findings were consistent after covariate adjustment, in sensitivity analyses, and for subgroups defined by age, enrollment location, and comorbidities. CONCLUSIONS: Outpatients infected with influenza A(H1N1)pdm09 or influenza B were more likely to be hospitalized than those with A(H3N2). Hospitalized patients infected with A(H1N1)pdm09 were younger and more likely to have severe disease at study entry (measured by ICU enrollment), but did not have worse 60-day outcomes

Urine lipoarabinomannan point-of-care testing in patients affected by pulmonary nontuberculous mycobacteria – experiences from the Danish Cystic Fibrosis cohort study

BACKGROUND: The urine lipoarabinomannan (LAM) strip test has been suggested as a new point-of-care test for active tuberculosis (TB) among human immunodeficiency virus (HIV) infected individuals. It has been questioned if infections with nontuberculous mycobacteria (NTM) affect assay specificity. We set forth to investigate if the test detects LAM in urine from a Danish cystic fibrosis (CF) population characterized by a high NTM prevalence and negligible TB exposure. METHOD: Patients followed at the Copenhagen CF Center were comprehensively screened for pulmonary NTM infection between May 2012 and December 2013. Urine samples were tested for LAM using the 2013 Determine™ TB LAM Ag strip test. RESULTS: Three-hundred and six patients had a total of 3,322 respiratory samples cultured for NTM and 198 had urine collected (65%). A total of 23/198 (12%) had active pulmonary NTM infection. None had active TB. The TB-LAM test had an overall positive rate of 2.5% applying a grade 2 cut-point as positivity threshold, increasing to 10.6% (21/198) if a grade 1 cut-point was applied. Among patients with NTM infection 2/23 (8.7%) had a positive LAM test result at the grade 2 cut-point and 9/23 (39.1%) at the grade 1 cut -point. Test specificity for NTM diagnosis was 98.3% and 93.1 for grade 2 and 1 cut-point respectively. CONCLUSIONS: This is the first study to assess urine LAM detection in patients with confirmed NTM infection. The study demonstrated low cross-reactivity due to NTM infection when using the recommended grade 2 cut-point as positivity threshold. This is reassuring in regards to interpretation of the LAM test for TB diagnosis in a TB prevalent setting. The test was not found suitable for NTM detection among patients with CF. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-014-0655-4) contains supplementary material, which is available to authorized users

Shifting paradigms of nontuberculous mycobacteria in cystic fibrosis

Important paradigms of pulmonary disease with nontuberculous mycobacteria (NTM) are currently shifting based on an increasing attention within the field of cystic fibrosis (CF). These shifts are likely to benefit the management of all patients with pulmonary NTM, regardless of underlying pathology. Currently several key areas are being revised: The first outbreak of human NTM transmission has been proven and new evidence of biofilm growth in vivo has been demonstrated. A better understanding of the clinical impact of NTM infection has led to increased diagnostic vigilance and new recommendations for lung transplantation are under way. While recent changes have reinvigorated the interest in NTM disease, the challenge remains, whether such advances can be successfully translated into improved management and care