Lung transplantation in patients with cystic fibrosis and Mycobacterium abscessus infection

AbstractMycobacterium abscessus lung disease is difficult to treat and has been considered a strong relative contraindication to lung transplantation. We performed double lung transplantation in three cystic fibrosis patients with ongoing, and a fourth with recent treatment for Mycobacterium abscessus lung infection. Despite prolonged antibiotic courses and adjustment of immunosuppressive therapy the first three patients developed skin infection and abscesses. At follow-up after 1, 3, 5 and 7years respectively no patient had evidence of M abscessus infection and all had stable lung function. Lung transplantation in patients with M abscessus lung infection is feasible but may involve severe complications

Dietary intake and nutritional status in a Scandinavian adult cystic fibrosis-population compared with recommendations

Malnutrition is a well-known complication in cystic fibrosis (CF). There is good evidence that maintaining a normal body-weight correlates well with improved survival in CF. Energy intake in excess of 120% of the estimated average requirement (EAR) has been advised since 1980s.To investigate the nutritional intake and status in the adult Scandinavian CF-population.A cross-sectional multi-centre study was used to investigate the nutritional status of 456 adult CF-patients (2003 2006). Height and weight were measured and body mass index (BMI) and z-scores were calculated. Pulmonary function was examined by dynamic spirometry. A 7-day pre-coded food record (FR) obtained energy and nutrient intake data in 180 patients.The mean energy intake was 114 (SD 30.0)% of EAR and thus significantly lower than the target of 120% EAR (p< 0.001) for patients with pancreatic insufficiency (PI) (n=136). Mean BMI was 22.0 (SD 2.9), the prevalence of BMI <18 was 13% and the prevalence of BMI ≥25 was 15% (n = 136). Mean BMI was 20.8 (SD 2.4) in PI-patients with FEV1 <70% and 23.2% (SD 3.0), in PI-patients with FEV1 ≥70%, mean difference 2.4, (95% CI: 1.5, 3.3) (p<0.001), but there was no difference in energy intake. BMI ≥18.5 and a reported energy intake <120% were revealed in 54% of the PI-patients.The energy intake did not reach the recommended 120% EAR, but the prevalence of underweight was lower than reported in other studies. The recommendation may exceed the requirement for a number of CF-patients. The nutritional status must still be closely monitored and nutritional advice and intervention should be individualised and adjusted to actual needs

Cystic fibrosis in adults. Diagnostic, epidemiologic and quality-of-life aspects

Background: Cystic fibrosis (CF) is a severe hereditary disease. The type of mutation in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene will determine the degree of CFTR chloride channel malfunction. Disturbed salt transport leads to production of sticky mucus, blocking exocrine gland ducts and persistent airway infection, starting early in life. Most patients are pancreatic insufficient, and almost all males are infertile due to obstruction of the vas deferens. Diagnostic criteria of CF are identification of two CF causing mutations and/or laboratory evidence of disturbed chloride transport in a patient with symptoms compatible with CF. Survival has increased due to improved care and today most patients are adult. CFTR mutations and elevated sweat chlorides are common in infertile men with congenital bilateral absence of the vas deferens (CBAVD). Aim: To address issues of importance for adults with CF; 1) review diagnosis of CF in adult age, 2) to find out if men with CBAVD, CFTR mutations and intermediate or elevated sweat chloride concentrations have evidence of early airway disease, 3) to analyze outcome of pregnancy and 4) to construct a health-related quality of life questionnaire. Methods: CF patients in Toronto (Paper I-IV), Göteborg and Lund (Paper IV) were included. Demographic, diagnostic and pregnancy data was extracted from the patient database and completed with chart review and patient interviews. Bronchoscopy with bronchoalveolar lavage (BAL) was performed in men with CBAVD, CFTR mutations and intermediate or elevated sweat chloride concentration. CF-related health issues were collected, a provisional questionnaire constructed and translated to Swedish, interviews with 135 patients performed in order to rank the items of importance to quality of life by frequency of occurrence and mean importance. The specific questionnaire was constructed based on the interview result. Results: In patients diagnosed as adults, pancreatic sufficiency, lung disease, inconclusive sweat test results and a high prevalence of uncommon mutations were common. Nasal potential difference measurement was a diagnostic aid. There was light growth of opportunistic gram-negative bacteria in BAL in 6/8 men with CBAVD. IL-8 and TNF alpha levels were higher in men with CBAVD. Absence of Burkholderia cenocepacia, pancreatic sufficiency and pre-pregnancy FEV1 > 50% of predicted was associated with better maternal survival. Pregnancy did not affect overall survival or decline in FEV1 when compared to the whole adult female CF population. The Cystic Fibrosis Quality of life Evaluative Self-administered Test (CF-QUEST) was constructed; CF-related health issues were collected. A provisional 114-item questionnaire was constructed and semi-structured interviews with adult CF patients in Toronto and Sweden were conducted. Items were ranked according to frequency of occurrence and mean rated importance. The final questionnaire was constructed based on the results. Conclusion: Diagnosis of CF in adults often requires extensive diagnostic methods. Some men presenting with CBAVD in adult age have a mild form of CF. Outcome is good for most pregnant women with CF. CF-QUEST is a new patient-derived HRQL instrument for adults with CF. Field studies to assess repeatability and responsiveness will follow

In vitro stimulation with nontuberculous mycobacteria induced a stronger cytokine response in leukocytes isolated from individuals with latent tuberculosis compared to those isolated from active tuberculosis or cystic fibrosis patients

Mycobacterium tuberculosis and opportunistic environmental non-tuberculous mycobacteria (NTM) can cause severe infection. Why latent tuberculosis infection advances to active disease, and why some individuals with cystic fibrosis (CF) develop pulmonary infections with NTM is still poorly understood. The aim of this study was to investigate the effector function of peripheral blood mononuclear cells (PBMC) from individuals with active or latent tuberculosis, individuals with CF with or without pulmonary NTM-infection and healthy controls, by measuring cytokine response to in vitro stimulation with different species of NTMs. The cytokine concentrations of IL-17A, IL-22, IL-23, IL-10, IL12p70 and IFN-γ were measured in PBMC-culture supernatants after stimulation with NTMs. PBMCs from individuals with latent tuberculosis infection showed strong IL-17A, IL-22, and IFN-γ responses compared to individuals with active tuberculosis or CF. IL-10 production was low in both tuberculosis groups compared to the CF groups and controls. This study suggests that IL-17A and IL-22 might be important to keep tuberculosis in a latent phase and that individuals with CF with an ongoing NTM infection seem to have a low cytokine response. © 2024 The AuthorsThis work was supported by The Swedish Government under the ALF agreement [grant number #95340] and with grants from Region Västra Gotaland, Sweden and Sahlgrenska University Hospital, Gothenburg, Sweden. </p

Molecular Epidemiology of Mycobacterium abscessus, with Focus on Cystic Fibrosis

Mycobacterium abscessus has been isolated increasingly often from the respiratory tracts of cystic fibrosis (CF) patients. It is not known whether these organisms are transmitted from person to person or acquired from environmental sources. Here, colony morphology and pulsed-field gel electrophoresis (PFGE) pattern were examined for 71 isolates of M. abscessus derived from 14 CF patients, three non-CF patients with chronic respiratory M. abscessus infection or colonization, one patient with mastoiditis, and four patients with infected wounds, as well as for six isolates identified as environmental contaminants in various clinical specimens. Contaminants and wound isolates mainly exhibited smooth colony morphology, while a rough colony phenotype was significantly associated with chronic airway colonization (P = 0.014). Rough strains may exhibit increased airway-colonizing capacity, the cause of which remains to be determined. Examination by PFGE of consecutive isolates from the same patient showed that they all represented a single strain, even in cases where both smooth and rough isolates were present. When PFGE patterns were compared, it was shown that 24 patients had unique strains, while four patients harbored strains indistinguishable by PFGE. Two of these were siblings with CF. The other two patients, one of whom had CF, had not had contact with each other or with the siblings. Our results show that most patients colonized by M. abscessus in the airways have unique strains, indicating that these strains derive from the environment and that patient-to-patient transmission rarely occurs

Clinical, economic, and societal burden of cystic fibrosis and the impact of the CFTR modulator, lumacaftor/ivacaftor : an assessment using linked registry data in Sweden

Aims We aimed to describe the clinical, economic, and societal burdens of cystic fibrosis (CF) and impact of CF transmembrane conductance regulator modulator (CFTRm) treatment on people with CF, caregivers, and healthcare systems. Material and methods This retrospective study used linked real-world data from Swedish national population-based registries and the Swedish CF Quality Registry to assess clinical, economic, and societal burden and CFTR impact in CF. Records from people with CF and a ten-fold control population without CF matched by sex, birth year, and location were compared during 2019. Outcomes for a subset aged &gt;6 years initiating lumacaftor/ivacaftor (LUM/IVA) in 2018 were compared 12 months pre- and post-treatment initiation. Results People with CF (n = 743) had &gt;10 times more inpatient and outpatient specialist visits annually vs controls (n = 7406). Those aged &gt;18 had an additional 77·7 (95% CI: 70·3, 85·1) days of work absence, at a societal cost of €11,563 (95% CI: 10,463, 12,662), while caregivers of those aged &lt;18 missed an additional 6.1 (5.0, 7.2) workdays. With LUM/IVA treatment, people with CF (n = 100) had significantly increased lung function (mean change in ppFEV1 [3·8 points; 95% CI: 1·1, 6·6]), on average 0·5 (95% CI: −0·8, −0·2) fewer pulmonary exacerbations and 45·2 (95% CI: 13·3, 77·2) fewer days of antibiotics. Days of work lost by caregivers of people with CF aged &lt;18 decreased by 5·4 days (95% CI: 2·9, 7·9). Conclusion CF is associated with a high clinical economic and societal burden in Sweden. Improvements in clinical status observed in people with CF treated with LUM/IVA were reflected in reduced caregiver and societal burden