J Hum Nutr Diet. 2022 Jan 28. doi: 10.1111/jhn.12991. Online ahead of print.

ABSTRACT

BACKGROUND: Cystic fibrosis (CF) primarily affects the lung, however, gastrointestinal disorders and symptoms, including dysbiosis, also impact on morbidity and quality of life. There is interest in strategies to modulate the gastrointestinal microbiota including probiotics, though evidence remains inadequate to guide practice, and information on use is limited. This research aimed to characterise probiotic use, beliefs and experiences of adults with CF.

METHODS: A cross-sectional questionnaire study was conducted in adults with CF (n=205) and a general population Control group (n=158), recruited from Victoria, Australia. Participants were classified as probiotic 'Ever Users' or 'Never Users'. Outcomes included self-reported probiotic use and factors associated with probiotic use, analysed using logistic regression analysis. Open-ended questionnaire responses were thematically analysed.

RESULTS: 70% of adults with CF had ever used probiotics (supplements and/or foods), comparable to Controls (80%), p=0.03. Key reasons for CF probiotic use were gastrointestinal- and antibiotic-related (75%). Most CF Ever Users (73%) did not discuss probiotic use with CF clinicians and 33% were uncertain if probiotics had been helpful. Female gender (OR, 95% CI) (2.82 (1.36-5.87, p=0.005)), university-level education (2.73 (1.24-6.01, p=0.01)) and bloating on antibiotics (2.14 (1.04-4.40, p=0.04)) were independently associated with probiotic use in CF; as was female gender in Controls (2.84 (1.20-6.71), p=0.02)).

CONCLUSION: Probiotics were used by adults with CF for gastrointestinal- and antibiotic-related reasons often without informing clinicians and despite uncertainty about perceived helpfulness. Further research investigating gastrointestinal outcomes of probiotics will inform practice recommendations guiding their use in CF and other chronic diseases. This article is protected by copyright. All rights reserved.

PMID:35092114 | DOI:10.1111/jhn.12991

Stem Cell Res. 2022 Jan 20;60:102683. doi: 10.1016/j.scr.2022.102683. Online ahead of print.

ABSTRACT

Cystic fibrosis (CF) is a genetic disease affects CFTR channel synthesis. While 90 percent of the CF patients now benefit from small molecule target therapies, this treatment has yet to extend to those bearing nonsense mutations. Studies of these rare mutations using cell lines with native pathological signatures of the disease may lead to breakthroughs in therapeutic development. Here, we report the generation of CF patient-derived induced pluripotent stem cells (iPSCs) carrying a nonsense mutation at position 308 (S308X). The pluripotency and genomic profile of the iPSC line was validated as a resource that can enable future research for CF.

PMID:35091309 | DOI:10.1016/j.scr.2022.102683

Lancet Infect Dis. 2022 Jan 25:S1473-3099(21)00586-7. doi: 10.1016/S1473-3099(21)00586-7. Online ahead of print.

ABSTRACT

The 2020 clinical practice guideline for the treatment of non-tuberculous mycobacterial pulmonary disease (NTM-PD) by the American Thoracic Society, European Respiratory Society, European Society of Clinical Microbiology and Infectious Diseases, and Infectious Diseases Society of America; and the 2017 management guideline by the British Thoracic Society covered pulmonary diseases in adults caused by Mycobacterium avium complex, Mycobacterium kansasii, Mycobacterium xenopi, and Mycobacterium abscessus. In order to provide evidence-based recommendations for the treatment of less common non-tuberculous mycobacterial (NTM) species in adult patients without cystic fibrosis or HIV infection, our expert panel group performed systematic literature searches to provide management guidance for pulmonary diseases caused by seven additional organisms: Mycobacterium chelonae, Mycobacterium fortuitum, Mycobacterium genavense, Mycobacterium gordonae, Mycobacterium malmoense, Mycobacterium simiae, and Mycobacterium szulgai. Treatment recommendations were developed by a structured consensus process. The evidence from the scientific literature published in English for treatment recommendations for pulmonary diseases caused by other NTM species was of very low quality, with the exception of M malmoense, and based on the evaluation of case reports and case series. For M malmoense, results from two randomised controlled trials and three retrospective cohort studies provided a better evidence base for treatment recommendations, although the evidence was still of low quality.

PMID:35090639 | DOI:10.1016/S1473-3099(21)00586-7

Front Biosci (Landmark Ed). 2022 Jan 13;27(1):19. doi: 10.31083/j.fbl2701019.

ABSTRACT

INTRODUCTION: Aerosolised drugs have been approved for several diseases such as cystic fibrosis and diabetes. Moreover; there are already drugs for pulmonary hypertension in aerosol form already on the market.

MATERIALS AND METHODS: Two drugs for pulmonary hypertension (Tadalafil and Macitentan) were milled and transformed from tablets to powder. Three different jet-nebulizers with seven different residual cups were combined. Moreover, we used 3 different ultrasound nebulizers with two different release methods.

RESULTS: The drug and residual cup designs produce alone or jointly different MMAD diameters. The three large (10 mls) residual cups with the jet-nebulisers produced the smallest aerosol droplets. Both ultrasound nebulisers are capable of producing optimal size aerosol droplets ≤5 μm mmad.

CONCLUSIONS: These two drugs can be easily administered as aerosol and an vivo clinical study will prove the safety for the airways.

PMID:35090324 | DOI:10.31083/j.fbl2701019

Int Forum Allergy Rhinol. 2022 Jan 28. doi: 10.1002/alr.22974. Online ahead of print.

ABSTRACT

BACKGROUND: Cystic fibrosis (CF) is a multi-system disease that often requires otolaryngology care. Individuals with CF commonly suffer from chronic rhinosinusitis but also present with hearing loss and dysphonia. Given these manifestations of CF, otolaryngologists are frequently involved in the care of the CF patient; however, there is limited consensus on optimal management of sinonasal, otologic and laryngologic symptoms.

METHODS: The CF Foundation convened a multidisciplinary team of otolaryngologists, pulmonologists, audiologists, pharmacists, a social worker, a nurse coordinator, a respiratory therapist, two adults with CF, and a caregiver of a child with CF to develop consensus recommendations. Workgroups developed draft recommendation statements based on a systematic literature review and a ≥80% consensus was required for acceptance of each recommendation statement.

RESULTS: The committee voted on 25 statements. 11 statements were adopted recommending a treatment or intervention, while 5 statements were formulated recommending against a specific treatment or intervention. The committee recommended 8 statements as an option for select patients in certain circumstances, and 1 statement did not reach consensus.

CONCLUSION: These multidisciplinary consensus recommendations will help providers navigate decisions related to Otolaryngology consultation, medical and surgical management of CF-CRS, hearing, and voice in individuals with CF. A collaborative and multidisciplinary approach is advocated to best care for our CF patients. Future clinical research is needed utilizing standardized, validated outcomes with comprehensive reporting of patient outcome, effects of modulator therapies, and genetic characteristics to help continue to advance care, decrease morbidity and improve the quality of life for individuals with CF. This article is protected by copyright. All rights reserved.

PMID:35089650 | DOI:10.1002/alr.22974

Indian J Pediatr. 2022 Jan 28. doi: 10.1007/s12098-021-04057-0. Online ahead of print.

ABSTRACT

Children with cystic fibrosis (CF) constitute a high-risk group for COVID-19 with underlying chronic lung disease. COVID-19 severity varying from mild infection to need of intensive care has been described in children with CF. Two children with significant underlying pulmonary morbidity are described here, who developed severe disease following SARS-CoV-2 infection. Case 1 (a 9-y-old boy) had pneumonia with respiratory failure requiring noninvasive ventilation support. He had delayed clearance of SARS-CoV-2, with recurrence of symptomatic disease with short asymptomatic period in between. He was also diagnosed with CF-related diabetes and allergic bronchopulmonary aspergillosis during the second episode. Case 2 (an 18-mo-old boy) had two episodes of SARS-CoV-2-related severe lower respiratory infection within a period of 2 mo, requiring high-flow nasal oxygen support. Both children had 3rd pulmonary exacerbation but SARS-CoV-2 was not detected in respiratory secretions. To conclude, children with CF with underlying pulmonary morbidity, can develop severe COVID-19 and prolonged SARS-CoV-2 shedding.

PMID:35089489 | DOI:10.1007/s12098-021-04057-0

Int J Behav Med. 2022 Jan 27. doi: 10.1007/s12529-022-10057-x. Online ahead of print.

ABSTRACT

BACKGROUND: Nutritional status and weight are closely linked to lung function and health status in cystic fibrosis (CF). The investigation of eating behaviours has shown mindfulness practices to be useful in modifying eating behaviours, particularly with obesity; to date, no research specifically explores how these concepts may be utilised within a CF population who face specific challenges in eating behaviours.

METHOD: Adult patients (n = 20, M = 8, age range 21-62 years) were recruited from a UK CF regional centre to take part in qualitative semi-structured interviews. Experiences of eating behaviours focusing on the use of mindful (or mindless) eating as barriers and enablers to achieving and maintaining optimal nutritional status were explored. Data were analysed using thematic analysis with a contextualist approach to understand how participants experienced eating behaviours within the context of health and weight status.

RESULTS: Participants engaged readily in discussions of eating behaviour describing active self-regulation of food eaten and calorie intake. Participants who struggled to maintain weight employed strategies to increase calorie intake such as distraction and multitasking while eating. Most participants reported no pleasure in food, describing eating as another treatment to endure. Confusion existed around how to eat healthily for CF alongside co-morbid health conditions including diabetes, cholesterol and heart disease.

CONCLUSION: Participants were highly aware of their eating behaviours, engaging in intentional and deliberate preparations, which could be described as mindful, for making eating a more automatic or mindless activity. Modifications to usual mindful eating interventions are needed to support people with CF.

PMID:35088244 | DOI:10.1007/s12529-022-10057-x

Pediatr Gastroenterol Hepatol Nutr. 2022 Jan;25(1):1-12. doi: 10.5223/pghn.2022.25.1.1. Epub 2022 Jan 7.

ABSTRACT

Inflammation plays an important role in the outcome of patients with cystic fibrosis (CF). It may develop due to cystic fibrosis transmembrane conductance regulator protein dysfunction, pancreatic insufficiency, or prolonged pulmonary infection. Fecal calprotectin (FC) has been used as a noninvasive method to detect inflammation. Therefore, the aim of the current meta-analysis was to investigate the relationship between FC and phenotype severity in patients with CF. In this study, searches were conducted in PubMed, Science Direct, Scopus, and Embase databases up to August 2021 using terms such as "cystic fibrosis," "intestine," "calprotectin," and "inflammation." Only articles published in English and human studies were selected. The primary outcome was the level of FC in patients with CF. The secondary outcome was the relationship between FC and clinical severity. Statistical analysis was performed using Comprehensive Meta-Analysis software. Of the initial 303 references, only six articles met the inclusion criteria. The mean (95% confidence interval [CI]) level of FC was 256.5 mg/dL (114.1-398.9). FC levels were significantly associated with pancreatic insufficiency (mean, 243.02; 95% CI, 74.3 to 411.6; p=0.005; I2=0), pulmonary function (r=-0.39; 95% CI, -0.58 to -0.15; p=0.002; I2=60%), body mass index (r=-0.514; 95% CI, 0.26 to 0.69; p<0.001; I2=0%), and Pseudomonas colonization (mean, 174.77; 95% CI, 12.5 to 337.02; p=0.035; I2=71%). While FC is a reliable noninvasive marker for detecting gastrointestinal inflammation, it is also correlated with the severity of the disease in patients with CF.

PMID:35087728 | PMC:PMC8762598 | DOI:10.5223/pghn.2022.25.1.1

Sci Rep. 2022 Jan 27;12(1):1540. doi: 10.1038/s41598-022-05446-x.

ABSTRACT

Primary cells isolated from the human respiratory tract are the state-of-the-art for in vitro airway epithelial cell research. Airway cell isolates require media that support expansion of cells in a basal state to maintain the capacity for differentiation as well as proper cellular function. By contrast, airway cell differentiation at an air-liquid interface (ALI) requires a distinct medium formulation that typically contains high levels of glucose. Here, we expanded and differentiated human basal cells isolated from the nasal and conducting airway to a mature mucociliary epithelial cell layer at ALI using a medium formulation containing normal resting glucose levels. Of note, bronchial epithelial cells expanded and differentiated in normal resting glucose medium showed insulin-stimulated glucose uptake which was inhibited by high glucose concentrations. Normal glucose containing ALI also enabled differentiation of nasal and tracheal cells that showed comparable electrophysiological profiles when assessed for cystic fibrosis transmembrane conductance regulator (CFTR) function and that remained responsive for up to 7 weeks in culture. These data demonstrate that normal glucose containing medium supports differentiation of primary nasal and lung epithelial cells at ALI, is well suited for metabolic studies, and avoids pitfalls associated with exposure to high glucose.

PMID:35087167 | DOI:10.1038/s41598-022-05446-x

Eur Respir J. 2022 Jan 27;59(1):2102209. doi: 10.1183/13993003.02209-2021. Print 2022 Jan.

NO ABSTRACT

PMID:35086845 | DOI:10.1183/13993003.02209-2021

Eur Respir J. 2022 Jan 27:2200022. doi: 10.1183/13993003.00022-2022. Online ahead of print.

NO ABSTRACT

PMID:35086838 | DOI:10.1183/13993003.00022-2022

Eur Respir J. 2022 Jan 27:2100508. doi: 10.1183/13993003.00508-2021. Online ahead of print.

ABSTRACT

RATIONALE: Cystic fibrosis (CF) is a monogenic life-shortening disease associated with highly variable individual disease progression which is difficult to predict. Here we assessed the association of forskolin-induced swelling (FIS) of patient-derived organoids (PDO) with long-term CF disease progression in multiple organs and compared FIS with the golden standard biomarker sweat chloride concentration (SCC).

METHODS: We retrieved 9-year longitudinal clinical data from the Dutch CF Registry of 173 people with mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Individual CFTR function was defined by FIS, measured as the relative size increase of intestinal organoids after stimulation with 0.8 µM forskolin, quantified as area under the curve (AUC). We used linear mixed effect models and multivariable logistic regression to estimate the association of FIS with long-term FEV1pp decline and development of pancreatic insufficiency, CF-related liver disease and diabetes. Within these models, FIS was compared with SCC.

RESULTS: FIS was strongly associated with longitudinal changes of lung function, with an estimated difference in annual FEV1pp decline of 0.32% (95%CI: 0.11%-0.54%; p=0.004) per 1000-points change in AUC. Moreover, increasing FIS levels were associated with lower odds of developing pancreatic insufficiency (adjusted OR: 0.18, 95%CI: 0.07-0.46, p<0.001), CF-related liver disease (adjusted OR: 0.18, 95%CI: 0.06-0.54, p=0.002) and diabetes (adjusted OR: 0.34, 95%CI: 0.12-0.97, p=0.044). These associations were absent for SCC.

CONCLUSION: This study exemplifies the prognostic value of a PDO-based biomarker within a clinical setting, which is especially important for people carrying rare CFTR mutations with unclear clinical consequences.

PMID:35086832 | DOI:10.1183/13993003.00508-2021

Eur Respir J. 2022 Jan 27:2103077. doi: 10.1183/13993003.03077-2021. Online ahead of print.

NO ABSTRACT

PMID:35086826 | DOI:10.1183/13993003.03077-2021

J Cyst Fibros. 2022 Jan 24:S1569-1993(22)00029-7. doi: 10.1016/j.jcf.2022.01.011. Online ahead of print.

ABSTRACT

BACKGROUND: Current guidelines recommend screening for Cystic Fibrosis (CF) related bone disease (CFBD) using dual-energy x-ray absorptiometry (DXA) for all people ≥ 18 years of age and select people ≥ 8 years of age. However, adherence to these guidelines is variable. This study aims to evaluate screening practices among adult programs in the US and identify patient and program-based characteristics which may influence screening.

METHODS: The CF Foundation Patient Registry (CFFPR) was used to identify all people over the age of 18 who were seen at adult CF programs and received screening for CFBD using DXA at least once between 2014 and 2018. Associations with patient and program level characteristics were assessed using the Chi Square test. Patient level variables were also examined using standardized difference to assess for meaningful clinical differences in rates of screening.

RESULTS: From 2014 to 2018, a total of 15,134 people over the age of 18 were identified in the CFFPR. Of these people, 9,023 (60%) received a DXA during the time period. The median rate of screening by program was 66% and programs in the highest quartile of screening obtained DXAs on >76% of their population. At the program level, larger size and increased adherence to other guideline practices such as OGTT screening and 4 visits, 4 cultures in a year correlated with higher rates of screening for CFBD. At the patient-level, people with lower lung function (FEV1 <90%) and those with CF related diabetes were more likely to be screened. People without health insurance were less likely to receive recommended screening.

CONCLUSION: Screening practices for CFBD vary widely across adult programs in the US despite recommendations to screen all people over the age of 18. Factors identified in this analysis may be used to identify those people at highest risk of missing appropriate screening. CFBD has significant implications for our patients and therefore routine screening should be emphasized as part of standard care moving forward.

PMID:35086791 | DOI:10.1016/j.jcf.2022.01.011

J Cyst Fibros. 2022 Jan 24:S1569-1993(22)00024-8. doi: 10.1016/j.jcf.2022.01.003. Online ahead of print.

ABSTRACT

OligoG has previously shown potentiation of aztreonam against Burkholderia cepacia complex (Bcc) through biofilm disruption. A randomized, double-blind, placebo-controlled cross-over design was used to evaluate safety and efficacy of inhaled OligoG as a therapy for Bcc-infected CF patients taking aztreonam. Subjects received OligoG (1050 mg daily) or matching placebo for 28-days. Of 14 subjects completing the study, 8 showed a mean decrease in total bacterial CFU's (0.82 log10) after OligoG treatment. There was a reduction in mean Bcc CFU's (2.19 log10) after OligoG treatment but this was not statistically significant. Rheology analysis showed improvements in phase-angle after OligoG, but there was no statistically significant improvement in lung function parameters. Six out of 12 QoL summary scores showed relative improvement after OligoG treatment compared to placebo. There was a favourable safety profile for OligoG. Potential for reducing Bcc warrants further investigation of OligoG for the treatment of infection in CF.

PMID:35086790 | DOI:10.1016/j.jcf.2022.01.003

Health Psychol Rev. 2022 Jan 28:1-29. doi: 10.1080/17437199.2022.2034516. Online ahead of print.

ABSTRACT

Adherence to medication in long-term conditions is around 50%. The key components of successful interventions to improve medication adherence remain unclear, particularly when examined over prolonged follow-up periods. Behaviour change theories are increasingly interested in the utility of habit formation for the maintenance of health behaviour change, but there is no documentation on how habit has been conceptualised in the medication adherence intervention literature, or what effect the key technique identified in habit formation theory (context dependent repetition) has in these studies. . To examine this, a machine-learning assisted review was conducted. Searches of MEDLINE, EMBASE and PSYCInfo and the reference list of a comprehensive systematic review of medication adherence interventions yielded 5973 articles. Machine learning-assisted title and abstract screening identified 15 independent RCTs published between 1976 and 2021, including 18 intervention comparisons of interest. Key findings indicate that conceptualisations of habit in the medication adherence literature are varied and intervention behaviour change techniques were diverse among these studies. Behaviour change technique coding identified only six studies which explicitly described using habit formation. Conclusions indicate that despite the potential utility of habits as a technique to support maintenance in medication adherence, randomised controlled trials of habit formation interventions are few. Future work should aim to develop this evidence base, drawing on contemporary habit theory and with explicit demonstration of what techniques have been used to promote habit formation.

PMID:35086431 | DOI:10.1080/17437199.2022.2034516

Monaldi Arch Chest Dis. 2022 Jan 27. doi: 10.4081/monaldi.2022.2087. Online ahead of print.

ABSTRACT

Early physiotherapy could play an important role in the management of severe COVID-19 subjects with consequences of prolonged ICU stay, although its effectiveness is still unclear. Aim of this study is to describe physiotherapy performed in severe COVID-19 patients and to evaluate its safety and feasibility. Consecutive adults with confirmed SARS-CoV-2 infection, admitted to the ICU, needing invasive mechanical ventilation for >24 hours and receiving early physiotherapy, have been enrolled. Adverse events occurred during physiotherapy sessions and timing and type of physiotherapy delivered were analysed, to identify the interventions most frequently performed and to determine the time taken to first mobilize, stand and walk. Functional and clinical assessment of patients was also performed at hospital discharge. Eighty-four severe COVID-19 subjects were enrolled. Few minor adverse events were recorded. Active mobilization was promoted over passive mobilization and independence in daily life activities was supported. Time interval from patients' intubation to the first physiotherapy treatment was 13 days and to walking was 27 days. Forty-eight (57.1%) subjects returned at home, whereas 29 (34.5%) were discharged to in-patient rehabilitation. Patients with tracheostomy experienced a delay in time from ICU admission until sit out of bed and ambulation, if compared with subjects without tracheostomy, although no differences were found in 6MWT and 1m-STST performances. This study reporting early physiotherapy during pandemic suggests that this intervention is feasible and safe for severe COVID-19 subjects, as well as healthcare workers, although delayed compared to other critically ill patients.

PMID:35086328 | DOI:10.4081/monaldi.2022.2087

J Biol Chem. 2022 Jan 24:101629. doi: 10.1016/j.jbc.2022.101629. Online ahead of print.

ABSTRACT

Pseudomonas aeruginosa is a gram-negative opportunistic human pathogen that is highly prevalent in individuals with cystic fibrosis (CF). A major problem in treating CF patients infected with P. aeruginosa is the development of antibiotic resistance. Therefore, the identification of novel P. aeruginosa antibiotic drug targets is of the utmost urgency. The genome of P. aeruginosa contains four putative cytochrome P450 enzymes (CYPs) of unknown function that have never before been characterized. Analogous to some of the CYPs from Mycobacterium tuberculosis, these P. aeruginosa CYPs may be important for growth and colonization of CF patients' lungs. In this study, we cloned, expressed, and characterized CYP168A1 from P. aeruginosa and identified it as a sub-terminal fatty acid hydroxylase. Spectral binding data and computational modeling of substrates and inhibitors suggest that CYP168A1 has a large, expansive active site and preferentially binds long chain fatty acids and large hydrophobic inhibitors. Furthermore, metabolic experiments confirm that the enzyme is capable of hydroxylating arachidonic acid, an important inflammatory signaling molecule present in abundance in the CF lung, to 19-hydroxyeicosatetraenoic acid (19-HETE; Km = 41 μM, Vmax = 220 pmol/min/nmol P450), a potent vasodilator which may play a role in the pathogen's ability to colonize the lung. Additionally, we found that the in vitro metabolism of arachidonic acid is subject to substrate inhibition and is also inhibited by the presence of the antifungal agent ketoconazole. This study identifies a new metabolic pathway in this important human pathogen that may be of utility in treating P. aeruginosa infections.

PMID:35085556 | DOI:10.1016/j.jbc.2022.101629

Am J Respir Crit Care Med. 2022 Jan 27. doi: 10.1164/rccm.202108-1911OC. Online ahead of print.

ABSTRACT

RATIONALE: Healthcare-associated transmission of nontuberculous mycobacteria (NTM) among people with cystic fibrosis (pwCF) has been investigated at CF Centers worldwide, with conflicting conclusions. We investigated transmission at the Colorado Adult CF Program.

OBJECTIVES: To systematically investigate healthcare-associated transmission and/or acquisition of NTM to determine similarity among respiratory and environmental isolates, and to compare home residence watershed mapping among pwCF having genetically similar NTM isolates.

METHODS: Whole genome sequencing (WGS) of NTM isolates from 80 pwCF was conducted to identify genetically similar isolate clusters (≤30 single nucleotide polymorphism differences). Epidemiological investigation, comparison of respiratory and environmental isolates, and home residence watershed mapping was analyzed.

MEASUREMENTS AND MAIN RESULTS: WGS analysis revealed 11 clusters of NTM (six Mycobacterium abscessus subspecies (ssp.) abscessus, one M. abscessus ssp. massiliense, two M. avium, and two M. intracellulare) among pwCF. Epidemiologic investigation demonstrated opportunities for healthcare-associated transmission in two M. abscessus and two M. avium clusters. Respiratory and healthcare environmental isolate comparisons revealed no genetic similarity. Individuals comprising one M. abscessus cluster, with no plausible healthcare-associated transmission, resided in the same watershed.

CONCLUSIONS: This study suggests healthcare-associated transmission of M. abscessus is rare and includes a report of potential healthcare-associated transmission of M. avium among pwCF. One M. abscessus cluster possibly had common acquisition from residing in the same watershed. Presence of genetically similar isolates is insufficient to demonstrate healthcare-associated NTM transmission. Standardizing epidemiologic investigation, combined with environmental sampling and watershed analysis, will improve understanding of the frequency and nature of healthcare-associated NTM transmission among pwCF.

PMID:35085056 | DOI:10.1164/rccm.202108-1911OC

Annu Rev Med. 2022 Jan 27;73:563-574. doi: 10.1146/annurev-med-042120-020148.

ABSTRACT

Cystic fibrosis (CF) is an autosomal recessive genetic disorder caused by mutations in CFTR, the cystic fibrosis transmembrane conductance regulator gene. People with CF experience a wide variety of medical conditions that affect the pulmonary, endocrine, gastrointestinal, pancreatic, biliary, and reproductive systems. Traditionally, CF carriers, with one defective copy of CFTR, were not thought to be at risk for CF-associated diseases. However, an emerging body of literature suggests that heterozygotes are at increased risk for many of the same conditions as homozygotes. For example, heterozygotes appear to be at increased risk for chronic pancreatitis, atypical mycobacterial infections, and bronchiectasis. In the United States alone, there are almost 10 million CF carriers. Universal newborn screening and prenatal genetic screening will identify more. Thus, there is a critical need to develop more precise estimates of health risks attributable to the CF carrier state across the lifespan.

PMID:35084992 | DOI:10.1146/annurev-med-042120-020148