Close monitoring and early intervention: management principles for cystic fibrosis in Denmark.

Cystic fibrosis (CF) care in Denmark has been characterized by close monitoring and pre-emptive treatment of lung disease and other CF-related complications. Continuous evaluation through data collection and commitment to clinical research has incrementally improved outcomes. This approach has been in line with best practices set forth by European Standards of Care but has also gone beyond Society standards particularly pertaining to early treatment with high-dose combination antimicrobial therapy. Despite a high prevalence of severe CF variants, lung function has been among the best in Europe. In this review, the Danish approach to management of CF prior to the introduction of new CF modulator treatment is explained and benchmarked. Downsides to the Danish approach are discussed and include increased burden of treatment, risk of antimicrobial resistance, side-effects and costs.

The impact of caring on caregivers of patients with life-threatening organ failure.

OBJECTIVES: This study aimed at characterizing 3 populations of family/friend caregivers of patients with different life-threatening organ failure regarding health-related quality of life, caregiver burden, and dyadic coping. METHODS: Three cross-sectional (population) studies were conducted at a tertiary hospital in Denmark (2019-2020). Patients with renal failure (RF), cystic fibrosis (CF), and intestinal failure (IF) were asked to designate the closest person with ≥18 years old involved in the care (caregiver) to participate in this study. Number of caregivers included were RF = 78, CF = 104, and IF = 73. Electronic questionnaires were filled in by caregivers to assess health-related quality of life and caregiver burden and by caregivers and respective patients to assess dyadic coping. RESULTS: The 3 caregiver groups had self-perception of poor health and energy; however, caregivers of CF patients perceived their physical role functioning better than those caregiving for RF and IF patients (p = 0.002). The level of caregiver burden was reported as not high, but caregivers used in average 13 hours/day for caring. Moreover, cleaning tasks (p = 0.005) and personal care (p = 0.009) were more demanding in RF and IF patients. Caregivers also did not differ regarding dyadic coping. When comparing patients and caregivers, stress communication by oneself and the partner differed (p < 0.001). SIGNIFICANCE OF RESULTS: Caregivers spent many hours in the care role, they reported poor health, and dyadic coping may be improved. Interventions in caregivers of patients with life-threatening organ failure could help to improve care management at home, caregiver's health, and dyadic coping between caregiver and patient and consequently reduce caregiver burden.

Bacterial Re-Colonization Occurs Early after Lung Transplantation in Cystic Fibrosis Patients.

Most cystic fibrosis (CF) patients referred for lung transplantation are chronically infected with Gram-negative opportunistic pathogens. It is well known that chronic infections in CF patients have a significant impact on lung-function decline and survival before transplantation. The rate and timing of re-colonization after transplantation have been described, but the impact on survival after stratification of bacteria is not well elucidated. We did a single-center retrospective analysis of 99 consecutive CF patients who underwent lung transplantation since the beginning of the Copenhagen Lung Transplant program in 1992 until October 2014. Two patients were excluded due to re-transplantation. From the time of CF diagnosis, patients had monthly sputum cultures. After transplantation, CF-patients had bronchoscopy with bronchoalveolar lavage at 2, 4, 6 and 12 weeks and 6, 12, 18 and 24 months after transplantation, as well as sputum samples if relevant. Selected culture results prior to and after transplantation were stored. We focused on colonization with the most frequent bacteria: Pseudomonas aeruginosa (PA), Stenotrophomonas maltophilia (SM), Achromobacter xylosoxidans (AX) and Burkholderia cepacia complex (BCC). Pulsed-field gel electrophoresis (PFGE) was used to identify clonality of bacterial isolates obtained before and after lung transplantation. Time to re-colonization was defined as the time from transplantation to the first positive culture with the same species. Seventy-three out of 97 (75%) had sufficient culture data for analyses with a median of 7 (1-91) cultures available before and after transplantation. Median colonization-free survival time was 23 days until the first positive culture after transplantation. After 2 years, 59 patients (81%) were re-colonized, 33 (48.5%) with PA, 7 (10.3%) with SM, 12 (17.6%) with AX, and 7 (10.3%) with BCC. No difference in survival was observed between the patients colonized within the first 2 years and those not colonized. Re-colonization of bacteria in the lower airways occurred at a median of 23 days after transplantation in our cohort. In our patient cohort, survival was not influenced by re-colonization or bacterial species.

Autologous fibrin sealant co-delivered with antibiotics is a robust method for topical antibiotic treatment after sinus surgery.

BACKGROUND: Most patients with cystic fibrosis have the risk of pathogenic bacteria being exchanged between their sinuses and lungs. AIMS: A method for topical application of antibiotics where the antibiotics persist for a long period of time is needed. MATERIAL AND METHODS: Ten patients with cystic fibrosis and bacterial sinusitis were included. Autologous platelet rich fibrin was mixed with an antibiotic solution and sprayed onto the mucosa at the end of an endoscopic sinus surgery; Colistin, a Ciprofloxacin-Colistin combination or Tobramycin was used. The antibiotic concentration was measured in the sinonasal mucus four, seven and 13 days after surgery. RESULTS: Nine patients had Pseudomonas aeruginosa in their nose/sinuses at the time of surgery; in eight of these P. aeruginosa was not detected by culture at the final visit. In the majority of the ten included patients the antibiotics were continuously released for more than 7 days. No severe side effects were seen. CONCLUSIONS: Autologous platelet rich fibrin co-delivered with antibiotics is a feasible method for topical antibiotic treatment in supplementary to sinus surgery. SIGNIFICANCE: We expect that this treatment is successful for eradication of sinonasal bacterial infections in immunosuppressed patients suffering from recalcitrant sinus infections. The efficacy should be evaluated in randomized controlled trials.

Cystic fibrosis newborn screening in Denmark: Experience from the first 2 years.

BACKGROUND: In Denmark, newborn screening (NBS) for cystic fibrosis (CF) was introduced on 1 May 2016. The implementation and results from the first 2 years of the national newborn CF screening program are presented. METHODS: The screening included immunoreactive trypsinogen (IRT), followed by evaluation for the F508del mutation when a value at or above the 50 ng/mL cutoff was present. In cases with a single F508del mutation or a very high IRT value above 145 ng/mL, next-generation sequencing of the CF transmembrane conductance regulator gene (CFTR) was performed. RESULTS: Of 126 522 newborn infants 126 338 were tested (99.85%), and 4730 samples (3.7%) were assessed for CFTR mutations. Twenty-six infants were screen-positive and referred for diagnostic follow-up of whom 22 were confirmed to have a CF diagnosis, four had one known and one CFTR allele with unknown pathogenicity, classified as cystic fibrosis screening positive inconclusive diagnosis (CFSPID), PPV 84.6%. One of the four children classified as CFSPID was later found to carry the two identified CFTR variants in cis and was reclassified as a carrier of CF. We found two false negatives; one exhibited an IRT level above the 50 ng/mL cutoff but was below the 145 ng/mL very high cutoff and with no F508del mutation present. The second false-negative fell below the 50 ng/mL IRT cutoff but was diagnosed shortly after birth on the basis of meconium ileus. Screening sensitivity, 91.7%. Two hundred thirty-two children were identified as carriers of CF, which is twofold above the estimated annual number of carriers. All but one carrier were heterozygous for the F508del CFTR mutation. Sixteen percent of the sequenced samples revealed rare CFTR variants, which were classified as nonpathogenic in relation to CF. CONCLUSIONS: During the first 2 years of NBS CF screening in Denmark, we identified close to the expected number of infants with CF using an algorithm based on IRT, presence of F508del mutation and comprehensive genetic analysis. CFSPID accounted for only a small minority, despite comprehensive CFTR sequencing, whereas more carriers than initially expected were identified.

Late diagnosis and poor nutrition in cystic fibrosis diagnosed before implementation of newborn screening.

AIM: Denmark has a high standard cystic fibrosis care. However, newborn screening was not implemented until 2016. This article describes the clinical status of cystic fibrosis patients at time of diagnosis prior to newborn screening. METHODS: Patients diagnosed with cystic fibrosis in Denmark in 2010-2014 were reviewed using the Danish Cystic Fibrosis Registry as well as patient files. Parameters collected were age at diagnosis, gender, weight, height, forced expiratory volume at 1 second, cystic fibrosis transmembrane regulator-genotype, lung bacteriology at diagnosis and previous diagnoses. RESULTS: A total of 63 patients were diagnosed in the study period. The most typical pre-cystic fibrosis diagnoses were asthma and pneumonia. The median age at diagnosis was 1.4 years for the pancreatic insufficient and 27.3 years for the pancreatic sufficient patients. Of the pancreatic insufficient patients, 21% had moderate to severe malnutrition with BMI below minus 2 SD and 40% had moderate to severe stunting with height below minus 2 SD. CONCLUSION: Diagnosis was delayed considerably compared to diagnosis by newborn screening in other countries. Many cystic fibrosis patients diagnosed due to clinical symptoms were moderately to severely underweight or stunted at diagnosis.

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. 471 individuals with a median of 104 FEV1 measurements per person and 7586 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.

Impact of cystic fibrosis on birthweight: a population based study of children in Denmark and Wales.

BACKGROUND: Poor growth during infancy and childhood is a characteristic feature of cystic fibrosis (CF). However, the impact of CF on intrauterine growth is unclear. We studied the effect of CF on birth weight in Denmark and Wales, and assessed whether any associations are due to differences in gestational age at birth. METHODS: We conducted national registry linkage studies in two countries, using data for 2.2 million singletons born in Denmark (between 1980 and 2010) and Wales (between 1998 and 2015). We used hospital inpatient and outpatient data to identify 852 children with CF. Using causal mediation methods, we estimated the direct and indirect (via gestational age) effect of CF on birth weight after adjustment for sex, parity and socioeconomic background. We tested the robustness of our results by adjusting for additional factors such as maternal smoking during pregnancy in subpopulations where these data were available. RESULTS: Babies with CF were more likely to be born preterm and with low birth weight than babies with no CF (12.7% vs 5% and 9.4% vs 5.8% preterm; 11.9% vs 4.2% and 11% vs 5.4% low birth weight in Denmark and Wales, respectively). Using causal mediation methods, the total effect of CF on birth weight was estimated to be -178.8 g (95% CI -225.43 to -134.47 g) in the Danish population and -210.08 g (95% CI -281.97 to -141.5 g) in the Welsh population. About 40% of this effect of CF on birth weight was mediated through gestational age. CONCLUSIONS: CF significantly impacts on intrauterine growth and leads to lower birth weight in babies with CF, which is only partially explained by shorter gestation.

The importance of early diagnosis of Mycobacterium abscessus complex in patients with cystic fibrosis.

Mycobacterium abscessus complex can cause severe lung infections and has proven to be a serious threat to patients with cystic fibrosis and a challenge for clinicians due to difficulties in timely diagnosis and complex multidrug treatment regimes. Mycobacterial culture is the gold standard for diagnosis, but in most cystic fibrosis centers it is performed less frequently than culture for other pathogens. Consensus today recommends just one annual mycobacterial culture for asymptomatic patients with cystic fibrosis, a strategy likely to lead to diagnostic delays. Postponement of diagnosis might be the deciding factor in whether an early colonization turns into chronic infection. This review highlights the latest developments in knowledge about the pathogenicity and clinical consequences of M. abscessus complex pulmonary disease, addressing the central theme of why pulmonary infection requires early identification and aggressive antibiotic treatment. The window of opportunity, before M. abscessus complex transforms from a mucosal colonizer to a chronic biofilm infection, is where microbial eradication is most likely to be successful, making early diagnosis essential for improved outcomes.

The effect of time-of-day and chest physiotherapy on multiple breath washout measures in children with clinically stable cystic fibrosis.

BACKGROUND: In this pilot study we investigated daytime variation of multiple breath nitrogen washout (N2MBW) measures in children with clinically stable cystic fibrosis. To our knowledge the effect of time-of-day on multiple breath washout measures in patients with cystic fibrosis has not previously been reported. Furthermore, we assessed the influence of chest physiotherapy on N2MBW measures. METHODS: Ten school children with cystic fibrosis performed N2MBW followed by spirometry and plethysmography in the morning and afternoon at three visits that were one month apart. Chest physiotherapy was performed immediately before the afternoon measurements at visit 2 and immediately before morning and afternoon measurements at visit 3. The influence of time-of-day and chest physiotherapy on the measures was evaluated using linear mixed models. RESULTS: There were adequate quality data from 8 children with median age (range) 9.6 (6.0; 15.1) years. Baseline lung clearance index (LCI) (range) was 9.0 (7.1; 13.0) and baseline FEV1% predicted was 97.5 (78.5; 117.9). No N2MBW measures were significantly influenced by time-of-day or chest physiotherapy. LCI (95% confidence interval) decreased non-significantly 0.05 (-0.32; 0.22) during the day and increased non-significantly 0.08 (-0.26; 0.42) after chest physiotherapy. All spirometric measures were unaffected by time-of-day and chest physiotherapy. For plethysmographic measures FRCpleth decreased significantly (p<0.01) 110 mL during the day, whereas a borderline significant (p = 0.046) decrease in ΔFRCpleth-MBW during the day and a borderline significant (p = 0.03) increase in TLC after CPT were observed. CONCLUSION: This study demonstrated that the time-of-day as well as chest physiotherapy performed immediately prior to N2MBW had no consistent or significant influence on N2MBW measures. However, we emphasize that further studies of the effect of both daytime variation and the effect of chest physiotherapy on multiple breath washout measures are warranted.

Can secretory immunoglobulin A in saliva predict a change in lung infection status in patients with cystic fibrosis? A prospective pilot study.

BACKGROUND: Chronic lung infection with Pseudomonas aeruginosa is the main cause of mortality in patients with cystic fibrosis (CF). Sinus colonization with P. aeruginosa often precedes intermittent lung colonization, and intermittent colonization precedes chronic infection.When P. aeruginosa colonizes the sinuses, elevated immunoglobulin A (IgA) levels specific against P. aeruginosa can be detected in saliva. Therefore, we hypothesized that increasing levels of IgA in saliva can be detected before P. aeruginosa lung colonization. METHODS: Forty-nine CF patients free from lung colonization with P. aeruginosa or other Gram-negative bacteria (GNB) were included in this prospective study. Saliva and serum samples were collected and examined for IgA antibodies against P. aeruginosa with at least 6-month intervals between sequential samples. RESULTS: A total of 110 measurements of IgA in saliva were included. During a median of 8.5-month follow-up, 25 patients changed their lung infection status. We were able to construct a statistical model that for a given value of IgA in saliva, could predict the probability of a change in lung infection status within the next 8.5 months (median): p = 1 / (1 + exp(-(-0.9582 + 1.6518*IgA)). The model includes a prediction band where 95% of new measurements are predicted to fall within. The model, however, failed to reach statistical significance (P = 0.056 1-tailed), probably because of lack of power. CONCLUSION: The saliva IgA model may predict a worsening in lung infection status presumably acting as a surrogate marker of P. aeruginosa bacterial sinusitis. The model may identify patients at risk of subsequent lung colonization and, thus, be a helpful clinical tool, but it should be tested in studies with larger sample sizes to evaluate its utility.

Prevalence and characteristics of chronic kidney disease among Danish adults with cystic fibrosis.

BACKGROUND: With improved prognosis of CF, comorbidities including chronic kidney disease (CKD) are becoming increasingly important. Identification of those at highest CKD risk is hence a priority. METHODS: In this cross-sectional study, adults with CF attending the Copenhagen CF Centre at Rigshospitalet with ≥2 measurements of serum creatinine from 2013 to 2015 were included. Data was obtained from an electronic CF database, which contains anonymised clinical and laboratory data on all individuals attending the clinic. CKD was defined as a confirmed (≥3months apart) estimated glomerular filtration rate≤60mL/min/1.73m2. RESULTS: Of 181 individuals, the CKD prevalence was 2.7% and increased to 11% after inclusion of lung transplanted patients. Individuals with CKD were generally older (median 39 (IQR, 36-45) vs. 31 (IQR, 24-39) years; p<0.001), diabetic (86% vs. 41%, p<0.001), with longer median duration of chronic pulmonary infection (28.3 (20.0-35.8) vs. 20.0 (9.9-34.7) years; p=0.008) and with longer intravenous aminoglycosides use (606 (IQR, 455-917) vs. 273 (IQR, 91-826) days, p=0.005). CONCLUSIONS: The CKD prevalence is high and related to age, diabetes, chronic infection, transplantation and aminoglycosides use. These observations call for longitudinal studies investigating CKD predictors in adults with CF.

Association between spirometry controlled chest CT scores using computer-animated biofeedback and clinical markers of lung disease in children with cystic fibrosis.

Background: Computed tomography (CT) of the lungs is the gold standard for assessing the extent of structural changes in the lungs. Spirometry-controlled chest CT (SCCCT) has improved the usefulness of CT by standardising inspiratory and expiratory lung volumes during imaging. This was a single-centre cross-sectional study in children with cystic fibrosis (CF). Using SCCCT we wished to investigate the association between the quantity and extent of structural lung changes and pulmonary function outcomes, and prevalence of known CF lung pathogens. Methods: CT images were analysed by CF-CT scoring (expressed as % of maximum score) to quantify different aspects of structural lung changes including bronchiectasis, airway wall thickening, mucus plugging, opacities, cysts, bullae and gas trapping. Clinical markers consisted of outcomes from pulmonary function tests, microbiological cultures from sputum and serological samples reflecting anti-bacterial and anti-fungal antibodies. Results: Sixty-four children with CF, median age (range) of 12.7 (6.4-18.1) years, participated in the study. The median (range) CF-CT total score in all children was 9.3% (0.4-46.8) with gas trapping of 40.7% (3.7-100) as the most abundant finding. Significantly higher median CF-CT total scores (21.9%) were found in patients with chronic infections (N = 12) including Gram-negative infection and allergic bronchopulmonary aspergillosis (ABPA) exhibiting CF-CT total scores of 14.2% (ns) and 24.0% (p < 0.01), respectively, compared to 8.0% in patients with no chronic lung infection. Lung clearance index (LCI) derived from multiple breath washout exhibited closest association with total CF-CT scores, compared to other pulmonary function outcomes. Conclusions: The most prominent structural lung change was gas trapping, while CF-CT total scores were generally low, both showing close association with LCI. Chronic lung infections, specifically in the form of ABPA, were associated with increased scores in lung changes. Further investigation of impact of infections with different microorganisms on extent and progression of structural CF lung disease is needed.

Boosting joint models for longitudinal and time-to-event data.

Joint models for longitudinal and time-to-event data have gained a lot of attention in the last few years as they are a helpful technique clinical studies where longitudinal outcomes are recorded alongside event times. Those two processes are often linked and the two outcomes should thus be modeled jointly in order to prevent the potential bias introduced by independent modeling. Commonly, joint models are estimated in likelihood-based expectation maximization or Bayesian approaches using frameworks where variable selection is problematic and that do not immediately work for high-dimensional data. In this paper, we propose a boosting algorithm tackling these challenges by being able to simultaneously estimate predictors for joint models and automatically select the most influential variables even in high-dimensional data situations. We analyze the performance of the new algorithm in a simulation study and apply it to the Danish cystic fibrosis registry that collects longitudinal lung function data on patients with cystic fibrosis together with data regarding the onset of pulmonary infections. This is the first approach to combine state-of-the art algorithms from the field of machine-learning with the model class of joint models, providing a fully data-driven mechanism to select variables and predictor effects in a unified framework of boosting joint models.

Phenotypic shift in Pseudomonas aeruginosa populations from cystic fibrosis lungs after 2-week antipseudomonal treatment.

BACKGROUND: The influence of suppressive therapy on the different P. aeruginosa phenotypes harbored in the lungs of cystic fibrosis (CF) patients remains unclear. Our aim was to investigate the phenotypic changes (mucoidy, hypermutability, antibiotic resistance, transcriptomic profiles and biofilm) in P. aeruginosa populations before and after a 2-week course of suppressive antimicrobial therapy in chronically infected CF patients in Denmark. MATERIAL AND METHODS: Prospective observational clinical study. Sputum samples were assessed before and after treatment for P. aeruginosa, with regard to: a) colony-forming units (CFU/mL), b) frequency of mucoids and non-mucoids, c) resistance pattern to anti-pseudomonal drugs, d) hypermutability, e) transcriptomic profiles, and f) presence of biofilms. RESULTS: We collected 23 sputum samples (12 before antibiotic treatment and 11 after) and 77 P. aeruginosa from different CF patients. After treatment, the P. aeruginosa burden diminished but antimicrobial resistance to aztreonam, tobramycin and ceftazidime rose; non-mucoid phenotypes presented increased resistance to colistin, tobramycin, meropenem, and ciprofloxacin, and hypermutable phenotypes to ciprofloxacin. In spite of biofilm persistence, a down-regulation of genes involved in denitrification was detected. CONCLUSION: A 2-week course of suppressive therapy reduces P. aeruginosa lung colonization and influences nitrogen metabolism genes, but also promotes antimicrobial resistance while P. aeruginosa persists in biofilms.

Sinus surgery can improve quality of life, lung infections, and lung function in patients with primary ciliary dyskinesia.

BACKGROUND: Chronic rhinosinusitis (CRS) and bacterial sinusitis are ubiquitous in patients with primary ciliary dyskinesia (PCD). From the sinuses, Pseudomonas aeruginosa can infect the lungs. METHODS: We studied the effect of endoscopic sinus surgery (ESS) on symptoms of CRS and lower airway infections in PCD patients in a prospective single-arm intervention study of ESS with adjuvant therapy using nasal irrigation with saline, topical nasal steroids, and 2 weeks of systemic antibiotics. Additional treatment with local colistin for 6 months was instigated when P. aeruginosa was cultured at ESS. RESULTS: Twenty-four PCD patients underwent ESS to search for an infectious focus (n = 10), due to severe symptoms of CRS (n = 8), or both (n = 6). Bacteria were cultured from sinus samples in 21 patients (88%), and simultaneous sinus and lung colonization with identical pathogens were observed in 13 patients (62%). Four patients with preoperative P. aeruginosa lung colonization (25%) had no regrowth during follow-up; 2 of these had P. aeruginosa sinusitis. Sinonasal symptoms were improved 12 months after ESS and we observed a trend toward better lung function after ESS. CONCLUSION: We demonstrated an improvement in CRS-related symptoms after ESS and adjuvant therapy. In selected PCD patients, the suggested regimen may postpone chronic lung infection with P. aeruginosa and stabilize lung function.

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.

Serodiagnosis of Mycobacterium abscessus complex infection in cystic fibrosis.

Early signs of pulmonary disease with Mycobacterium abscessus complex (MABSC) can be missed in patients with cystic fibrosis (CF). A serological method could help stratify patients according to risk. The objective of this study was to test the diagnostic accuracy of a novel method for investigating IgG activity against MABSC.A prospective study of all patients attending the Copenhagen CF Centre was conducted by culturing for MABSC during a 22-month period and then screening patients with an anti-MABSC IgG ELISA. Culture-positive patients had stored serum examined for antibody kinetics before and after culture conversion.307 patients had 3480 respiratory samples cultured and were then tested with the anti-MABSC IgG ELISA. Patients with MABSC pulmonary disease had median anti-MABSC IgG levels six-fold higher than patients with no history of infection (434 versus 64 ELISA units; p<0.001). The test sensitivity was 95% (95% CI 74-99%) and the specificity was 73% (95% CI 67-78%). A diagnostic algorithm was constructed to stratify patients according to risk.The test accurately identified patients with pulmonary disease caused by MABSC and was suited to be used as a complement to mycobacterial culture.

Epidemiology of nontuberculous mycobacteria among patients with cystic fibrosis in Scandinavia.

BACKGROUND: Nontuberculous mycobacteria (NTM) are an emerging threat to cystic fibrosis (CF) patients but their epidemiology is not well described. METHODS: In this retrospective observational study we identified all Scandinavian CF patients with a positive NTM culture from airway secretions from 2000 to the end of 2012 and used national CF databases to describe microbiological and clinical characteristics. RESULTS: During the 13-year period 157 (11%) CF patients were culture positive for NTM at least once. Mycobacterium abscessus complex (MABSC) (45%) and Mycobacterium avium complex (MAC) (32%) were the predominant species with geographical differences in distribution. Younger patients were more prone to MABSC (p<0.01). Despite treatment, less than one-third of MABSC patients with repeated positive cultures cleared their infection and a quarter had a lung transplant or died. CONCLUSION: NTM are significant CF pathogens and are becoming more prevalent in Scandinavia. MABSC and MAC appear to target distinct patient groups. Having multiple positive cultures despite treatment conveys a poor outcome.