J Clin Transl Endocrinol. 2022 Jul 28;29:100303. doi: 10.1016/j.jcte.2022.100303. eCollection 2022 Sep.

NO ABSTRACT

PMID:35928247 | PMC:PMC9344016 | DOI:10.1016/j.jcte.2022.100303

Ital J Pediatr. 2022 Aug 4;48(1):141. doi: 10.1186/s13052-022-01331-5.

ABSTRACT

Cystic fibrosis (CF) is the most common inherited disease in Caucasian populations, affecting around 50,000 patients in Europe and 30,000 in United States. A mutation in CF trans-membrane conductance regulator (CFTR) gene changes a protein (a regulated chloride channel), which is expressed in many tissues. Defective CFTR results in reduced chloride secretion and an overage absorption of sodium across the epithelia, leading to thickened secretions in organs such as pancreas and lung. Gradually, there have been considerable improvements in the survival of people with CF, thanks to substantial changes in specialized CF care and the discovery of new CFTR modulators drugs. Nevertheless, lung disease remains the most common cause of death. For these reasons improvement of sputum clearance is a major therapeutic aim in CF. So far, symptomatic mucolytic therapy is mainly based on inhalation of dornase alfa, hypertonic saline or mannitol, in combination with physiotherapy. The major component of mucus in CF is pus including viscous material such as polymerized DNA derived from degraded neutrophils. Dornase alfa cleaves the DNA released from the neutrophils and reduces mucous viscosity, and further prevent airway infections and damage to the lung parenchyma. In this review we will summarize the current knowledge on dornase alfa in the treatment of CF lung disease, especially highlighting the positive effect on lung clearance index, a sensitive measure of ventilation inhomogeneity.

PMID:35927765 | DOI:10.1186/s13052-022-01331-5

Pediatr Pulmonol. 2022 Aug 4. doi: 10.1002/ppul.26093. Online ahead of print.

ABSTRACT

Access to CFTR modulators has been gradually increasing for people with cystic fibrosis, the first of which was ivacaftor, a CFTR potentiator which is part of all clinically available modulator treatments. In this study, we hypothesized that the steady-state concentrations in blood and tissue are highly variable in patients taking ivacaftor in a real-world context, which may have impacts on treatment approach. We collected nasal epithelial cells to estimate target site concentrations and blood samples to estimate pharmacokinetic parameters at steady state. We found that patients on ivacaftor monotherapy have variable concentrations well above the maximal effective concentration and may maintain concentrations necessary for clinical benefit even if dosing is reduced. We also are the first to provide detailed target site concentration data over time, which shows that tissue concentrations do not fluctuate significantly and do not correlate with plasma concentrations. These findings show that some patients may have higher-than-expected concentrations and may benefit from tailored dosing to balance clinical response with side effects or adherence needs. This article is protected by copyright. All rights reserved.

PMID:35927224 | DOI:10.1002/ppul.26093

Pediatr Pulmonol. 2022 Aug 4. doi: 10.1002/ppul.26087. Online ahead of print.

ABSTRACT

BACKGROUND: The spread of COVID-19 was associated with increased stress and new mental health concerns for people with cystic fibrosis (pwCF), already at increased risk for depression and anxiety. This study assessed stress and mental health in adolescents and young adults with CF one year from when the pandemic began.

METHODS: Sixty-six pwCF (mean age=24; range 14-36) completed a new measure of the impact of COVID-19 (COVID-19 Exposure and Family Impact Scale-Adolescence and Young Adult; CEFIS-AYA); the Patient Health Questionnaire-9, and the Generalized Anxiety Disorder-7. The Italian translation of the CEFIS-AYA was performed.

RESULTS: On the CEFIS-AYA, the mean Exposure score was 5.2 (SD=2.6) out of 28. The mean Impact score was 1.8 (SD=0.7; negative valence >2.5). Individuals were more sedentary and undertaking less exercise. Average stress rating was 5.9 (SD=2), indicating moderate stress. No significant differences were found between those who did (N=12) vs did not have a COVID infection (N=54). A high percentage of participants scored above the clinical cut-off for depression (45%) and anxiety (41%), with a low proportion reporting moderate-severe symptomatology.

CONCLUSION: After one-year, the pandemic was having a less significant impact on patients' daily lives. Sedentary activity and reduced exercise were common. Despite expectations that this group was particularly vulnerable, depression and anxiety scores were similar to the rates described for this population prior to the pandemic. Overall, these results suggested that pwCF are highly resilient and nearly one year after the onset of COVID-19, have returned to similar daily activities and emotional health. This article is protected by copyright. All rights reserved.

PMID:35927222 | DOI:10.1002/ppul.26087

Zhonghua Jie He He Hu Xi Za Zhi. 2022 Aug 12;45(8):739-752. doi: 10.3760/cma.j.cn112147-20220407-00290.

ABSTRACT

Pseudomonas aeruginosa (PA) is the second common Gram-negative bacterium for hospital acquired pneumonia (HAP) in China (16.9%-22.0%). The proportion of PA in community acquired pneumonia (CAP) was about 1.0%, while increased to 1.8%-8.3% in severe CAP. PA accounted for 67.0% of CAP in patients with a history of PA infection, bronchiectasis, very severe chronic obstructive pulmonary disease (COPD) or tracheotomy. Considering the high disease burden of lower respiratory tract infections (LRTIs) caused by PA, together with the progress in this field in recent years, the Pulmonary Infection Assembly of Chinese Thoracic Society updated the "Chinese expert consensus on the management of lower respiratory tract infections of Pseudomonas aeruginosa in adults (2014 version)", focusing on pathogen detection, diagnosis, antimicrobial therapy, comprehensive management, infection prevention and control.PA causes both acute and chronic LTRIs. Acute LRTIs mainly include pneumonia (CAP, HAP and ventilator-associated pneumonia), tracheobronchitis, lung abscess and empyema. The diagnosis of chronic LTRIs should be based on a comprehensive assessment of (1) underlying chronic structural lung diseases, such as bronchiectasis, cystic fibrosis, COPD, or immunocompromised conditions; (2) the presence of clinical manifestations of LRTIs; and (3) ≥ two times (at least 3 months apart) of PA detected from eligible lower respiratory tract specimens within 1 year. It is important to distinguish infection from colonization when PA is isolated from lower respiratory tract specimens. Drug susceptibility test is a conventional method for PA resistance detection and serves as a basis for target therapy. When drug susceptibility test shows limited activity of available agents, combined susceptibility test is suggested to select antimicrobial drugs with additive or synergistic effect in vitro for combination therapy. Rapid test of resistance mechanisms of PA isolates, such as carbapenemase phenotype confirmation tests, is recommended if available. It is recommended not to routinely detect resistance genes for choosing therapeutic agents.For patients with acute LRTIs in critical condition or with high risk factors for PA infection, empirical antimicrobial therapy covering PA should be initiated after collecting specimens for microbiological tests. In patients with suspected PA pneumonia who are not critically ill, single antimicrobial drug of anti-PA activity with high lung concentration should be selected for empirical treatment. However, for patients with a serious condition such as sepsis or with risk factors for multidrug-resistant (MDR) PA, a combination of two different classes of antimicrobial drugs that are both potentially susceptible should be used. The antimicrobial regimen should follow pharmacokinetics/pharmacodynamics principles to ensure adequate dosage and administration frequency. For confirmed PA LRTIs, antibiotics should be selected based on drug sensitivity. In patients without significant underlying diseases, single therapy of an active antimicrobial with adequate pulmonary concentration is recommended rather than combination therapy; when all the available active agents have poor intrapulmonary concentrations, combination therapy is obligatory. For LRTIs caused by carbapenem-resistant PA (CRPA) or difficult-to-treat resistance PA (DTR-PA), if an agent of new enzyme inhibitor, such as ceftolozane/tazobactam, ceftazidime/avibactam, and imipenem/cilastatin/relebactam shows in vitro sensitivity, it is recommended as the first-line choice; cefiderocol may serve as the second-line treatment. Combination therapy based on polymyxins may also be considered. Other potentially successful approaches for drug-resistant PA LRTIs include extended infusion time of β-lactams, combination therapy and inhaled antimicrobial therapy.In patients with underlying chronic structural lung diseases, the antimicrobial regimen (drug, dosage, route of administration, and duration of therapy) should be decided according to clinical features, drug sensitivity, and treatment goals (control of exacerbated symptoms, eradication of new-emerging PA, or prevention of flare-ups in patients with frequent exacerbation).Along with antimicrobial therapy, comprehensive care including airway clearance therapy (ACT), oxygen therapy, nutritional support and organ function protection should be provided. From the perspective of nosocomial infection prevention and control, isolation and prophylaxis of contact transmission are recommended to block PA transmission in addition to standard prevention measures. Targeted active screening, timely monitoring and feedback can help the prevention and control of MDR-PA. The systemic and topical use of prophylactic antimicrobials is not recommended.

PMID:35927044 | DOI:10.3760/cma.j.cn112147-20220407-00290

Zhonghua Jie He He Hu Xi Za Zhi. 2022 Aug 12;45(8):733-735. doi: 10.3760/cma.j.cn112147-20220530-00464.

ABSTRACT

Pseudomonas aeruginosa is one of the most important pathogens causing chronic lower respiratory tract infections in patients with chronic lung diseases such as cystic fibrosis, bronchiectasis and chronic obstructive pulmonary disease. The poor prognosis of these diseases has been found to be associated with chronic Pseudomonas aeruginosa infection in lower respiratory tract, which can be a consequence or a cause of the disease progression depending on different circumstances. Optimizing the management of chronic Pseudomonas aeruginosa infection is of great significance to improve the prognosis of these chronic lung diseases. Unlike the therapy of acute pneumonia due to Pseudomonas aeruginosa, the goals of the management for chronic Pseudomonas aeruginosa infection are not only to control infection, but also to reduce symptoms, prevent exacerbations, stop the disease progression and improve the quality of life. In addition to systemic anti-pseudomonas therapy during exacerbations, long-term multiple measures including anti-inflammatory therapy, immunomodulatory therapy,airway clearance techniques, mucoactive therapy, etc. should also be given to the patients with chronic lower respiratory tract infection due to Pseudomonas aeruginosa.

PMID:35927042 | DOI:10.3760/cma.j.cn112147-20220530-00464

Eur Respir J. 2022 Aug 4;60(2):2201040. doi: 10.1183/13993003.01040-2022. Print 2022 Aug.

NO ABSTRACT

PMID:35926867 | DOI:10.1183/13993003.01040-2022

Respir Med. 2022 Jul 21;201:106937. doi: 10.1016/j.rmed.2022.106937. Online ahead of print.

ABSTRACT

BACKGROUND: Non cystic fibrosis, non primary ciliary dyskinesia bronchiectasis (nCFnPCD-BE) results in significant morbidity with few evidence-based treatments.

OBJECTIVE: assessments are required to assess severity and evaluate treatment. Lung clearance index (LCI) measures ventilation inhomogeneity and is a sensitive test of disease in CF; its use in nCFnPCD-BE is unclear.

METHODS: A systematic review of LCI in nCFnPCD-BE was performed using standard methodology (protocol registered on PROSPERO, University of York).

RESULTS: Of 276 records identified, 12 articles, describing 519 adult and paediatric patients in cross-sectional studies were included, addressing several domains. 1: What is the utility of LCI in detecting disease and severity? LCI detected disease in adults, differentiating bronchiectasis from controls (AUC 0.90 to 0.96) and mild from moderate/severe bronchiectasis on CT (AUC 0.73). 2: Does LCI correlate with spirometry and imaging? LCI correlated with spirometry in adult (r = -0.37 to -0.61) and paediatric (r = -0.6) groups, signs of bronchiectasis on CT, and CT scoring systems (modified Reiff). 3: Does LCI relate to subjective scores of severity? In adults, LCI correlated with St. George's Respiratory Questionnaire (r = 0.18) and Bronchiectasis Severity Index (r = 0.45). 4: Does LCI identify response to intervention? LCI did not change in studies examining LCI pre-post intervention (adults treated for exacerbation and undergoing physiotherapy). Overall study quality was variable.

CONCLUSION: Contrary to data in CF, the review did not identify good quality studies defining the role of LCI in children with bronchiectasis. In adults, LCI was a sensitive measure of disease severity and correlated with clinical assessment tools.

PMID:35926429 | DOI:10.1016/j.rmed.2022.106937

Front Pediatr. 2022 Jul 18;10:941785. doi: 10.3389/fped.2022.941785. eCollection 2022.

ABSTRACT

BACKGROUND: Children and adolescents seem to be less affected by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease in terms of severity, especially until the increasing spread of the omicron variant in December 2021. Anatomical structures and lower number of exhaled aerosols may in part explain this phenomenon. In a cohort of healthy and SARS-CoV-2 infected children, we compared exhaled particle counts to gain further insights about the spreading of SARS-CoV-2.

MATERIALS AND METHODS: In this single-center prospective observational trial, a total of 162 children and adolescents (age 6-17 years), of whom 39 were polymerase chain reaction (PCR)-positive for SARS-CoV-2 and 123 PCR-negative, were included. The 39 PCR-positive children were compared to 39 PCR-negative age-matched controls. The data of all PCR-negative children were analyzed to determine baseline exhaled particle counts in children. In addition, medical and clinical history was obtained and spirometry was measured.

RESULTS: Baseline exhaled particle counts were low in healthy children. Exhaled particle counts were significantly increased in SARS-CoV-2 PCR-positive children (median 355.0/L; range 81-6955/L), compared to age-matched -negative children (median 157.0/L; range 1-533/L; p < 0.001).

CONCLUSION: SARS-CoV-2 PCR-positive children exhaled significantly higher levels of aerosols than healthy children. Overall children had low levels of exhaled particle counts, possibly indicating that children are not the major driver of the SARS-CoV-2 pandemic.

TRIAL REGISTRATION: [ClinicalTrials.gov], Identifier [NCT04739020].

PMID:35923787 | PMC:PMC9339682 | DOI:10.3389/fped.2022.941785

Cureus. 2022 Jul 2;14(7):e26511. doi: 10.7759/cureus.26511. eCollection 2022 Jul.

ABSTRACT

Background Self-efficacy is an important determinant of treatment adherence, and peer modelling of success can provide vicarious self-efficacy. A series of patient stories ('talking heads' videos) were developed with people with cystic fibrosis (CF) as part of the CFHealthHub multi-component adherence intervention, aiming to demonstrate success with daily therapy in 'people like me'. Methodology One-to-one semi-structured interviews exploring patients' experiences, barriers and facilitators of nebuliser adherence were audio and video-recorded between October 2015 and August 2016. Interview transcripts were reviewed to identify descriptions of problem-solving and sustained treatment success. Positive stories potentially providing vicarious descriptions of success were selected as video clips. Results In total, 14 adults with CF were recruited from five UK CF centres. Each participant contributed a median of five (interquartile range: 3-6) video clips, and a total of 57 unique clips were uploaded onto the CFHealthHub digital platform. Nine of those clips spanned two categories, hence, there were 66 clips across 16 categories. Conclusions The videos were well received though some adults were concerned that comparisons with peers might create anxiety by highlighting the possibility of future decline or current relative underperformance. It is important to sensitively support choice when providing resources aiming to increase vicarious self-efficacy. Our experience may guide the development of similar videos for people with other long-term conditions.

PMID:35923485 | PMC:PMC9342668 | DOI:10.7759/cureus.26511

Life Sci Alliance. 2022 Aug 3;5(12):e202101320. doi: 10.26508/lsa.202101320. Print 2022 Dec.

ABSTRACT

Cystic fibrosis is caused by genetic defects that impair the CFTR channel in airway epithelial cells. These defects may be overcome by specific CFTR modulating drugs, for which the efficacy can be predicted in a personalized manner using 3D nasal-brushing-derived airway organoids in a forskolin-induced swelling assay. Despite of this, previously described CFTR function assays in 3D airway organoids were not fully optimal, because of inefficient organoid differentiation and limited scalability. In this report, we therefore describe an alternative method of culturing nasal-brushing-derived airway organoids, which are created from an equally differentiated airway epithelial monolayer of a 2D air-liquid interface culture. In addition, we have defined organoid culture conditions, with the growth factor/cytokine combination neuregulin-1β and interleukin-1β, which enabled consistent detection of CFTR modulator responses in nasal-airway organoid cultures from subjects with cystic fibrosis.

PMID:35922154 | DOI:10.26508/lsa.202101320

ANZ J Surg. 2022 Aug 3. doi: 10.1111/ans.17948. Online ahead of print.

ABSTRACT

Cystic fibrosis (CF) is a complex multiorgan disease, which often affects the gastrointestinal tract. With improved CF specific therapies and multidisciplinary management, patients with CF are now living longer with a median life expectancy of around 50 years. This increased life expectancy has resulted in corresponding increase in presentations of the CF patient with comorbid surgical conditions that were never important considerations. Investigations and management of these conditions, such as distal intestinal obstruction syndrome and colorectal cancer warrant good clinical understanding of the unique challenges that CF patients present including chronic immunosuppression, impaired respiratory function and their multi-organ dysfunction. The purpose of this review is to provide general surgeons with a contemporary update on the CF related surgical issues as they are likely to become increasingly involved in the care of these complex patients and form an integral part of the multidisciplinary team.

PMID:35920692 | DOI:10.1111/ans.17948

Eur J Radiol. 2022 Jul 27;154:110454. doi: 10.1016/j.ejrad.2022.110454. Online ahead of print.

ABSTRACT

OBJECTIVES: Patients with cystic fibrosis (CF) increasingly require imaging for the diagnosis of abdominal complications. We prospectively evaluated the image quality and signal-to-noise ratio (SNR) of a modern radial volumetric encoding (RAVE) T2/T1 hybrid sequence for abdominal magnetic resonance imaging (MRI). RAVET2/T1 is a three-dimensional radial sequence with fat saturation and blood flow suppression that acquires T2- and T1-weighted contrasts in one scan in an identical slice position during free-breathing.

METHODS: Sixteen CF patients underwent axial T2 HASTE (1000 ms/93 ms TR/TE), T1 DIXON (6.8 ms/2.4 ms/4.8 ms TR/TE1/TE2), and RAVE T2/T1 hybrid sequence (1200 ms/1.7 ms/3.3 ms/4.9 ms/102 ms TR/TE1/TE2/TE3/TE4) of the upper abdomen at 1.5 Tesla. The SNR values in six different regions were assessed and compared using the Wilcoxon signed-rank test. The image quality criteria were rated on a 5-point Likert scale.

RESULTS: In all regions, the SNR was significantly higher in the T2 weighted aspect of the RAVE T2/T1 hybrid sequence compared to T2 HASTE (p < 0.05) and significantly lower in the T1 weighted in-phase aspect of the RAVE T2/T1 hybrid sequence compared to the T1 DIXON sequence (p < 0.05). Qualitatively the T2 weighted aspect of the RAVE T2/T1 hybrid sequence was rated significantly higher than the T2 HASTE in 6 of 7 categories (p < 0.05) and the T1 weighted in-phase aspect of the RAVE T2/T1 hybrid sequence was rated significantly higher than the T1 DIXON in 2 of 6 categories (p < 0.05).

CONCLUSIONS: The abdominal radial RAVE T2/T1 hybrid sequence provided higher image quality and SNR than the T2HASTEsequence. Together with increased robustness against motion artifacts, the RAVE T2/T1 hybrid sequence appears to be a good tool for abdominal imaging in CF patients.

PMID:35917758 | DOI:10.1016/j.ejrad.2022.110454

JBRA Assist Reprod. 2022 Aug 1. doi: 10.5935/1518-0557.20220012. Online ahead of print.

ABSTRACT

OBJECTIVE: Genetic counseling and carrier screening are part of the gamete donation process by healthy individuals. We aim to review the findings of genetic counseling and carrier screening of a cohort of candidates at our public gametes bank.

METHODS: Thirty-four male and 64 female candidates had genetic counseling with a medical geneticist before donation. Of these, one female candidate voluntarily dropped-out. Thirty-four males and 63 females performed karyotype and screening for the more common pathogenic variants for CFTR-related cystic fibrosis and spinal muscular atrophy (SMN1) in the Portuguese population. In addition, all females also performed Fragile X expansion screening (FMR1). Thirty candidates with known or assumed African ancestry performed hemoglobinopathies screening.

RESULTS: Six candidates were definitely or temporarily withheld from the donation process given their family or personal history that required further investigation. Of 97 candidates tested, 16.5% presented anomalous laboratory results (16/97): ten candidates were carriers for an autosomal recessive disorder - cystic fibrosis (5/97), sickle cell anemia (3/30), and spinal muscular atrophy (2/97). One female was an FMR1 pre-mutation carrier (1/63). One female candidate presented with triple X mosaicism: 47,XXX[2]/46,XX[50]. Two candidates presented with chromosomal instability of unknown origin. In one candidate, a mosaic for the Philadelphia chromosome was detected, revealing the diagnosis of chronic myeloid leukemia.

CONCLUSIONS: From a cohort of 97 candidates, 21.7% had a family/personal history or an anomalous laboratory result that required additional genetic counseling, stressing the importance of performing pre-donation genetic counseling in this population.

PMID:35916466 | DOI:10.5935/1518-0557.20220012

Reproduction. 2022 Jul 14;164(3):R47-R56. doi: 10.1530/REP-21-0315. Print 2022 Sep 1.

ABSTRACT

IN BRIEF: The genetic heterogeneity of CFTR gene mutations in Chinese patients with congenital absence of the vas deferens (CAVD) differs from the hotspot mutation pattern in Caucasians. This paper reviews and suggests a more suitable screening strategy for the Chinese considering the dilemma of CFTR genetic blocking.

ABSTRACT: Congenital absence of the vas deferens (CAVD) is a major cause of obstructive azoospermia and male infertility, with CFTR gene mutation as the main pathogenesis. Other genes such as ADGRG2, SLC9A3, and PANK2 have been discovered and proven to be associated with CAVD in recent studies. Multiple CFTR hotspot mutations have been found in Caucasians in several foreign countries, and relevant genetic counseling and preimplantation genetic diagnosis (PGD) have been conducted for decades. However, when we examined research on Chinese CAVD, we discovered that CFTR mutations show heterogeneity in the Chinese Han population, and there is currently no well-established screening strategy. Therefore, we have reviewed the literature, combining domestic and international research as well as our own, aiming to review research progress on the CFTR gene in China and discuss the appropriate scope for CFTR gene detection, the detection efficiency of other CAVD-related genes, and the screening strategy applicable to the Chinese Han population. This study provides more valuable information for genetic counseling and a theoretical basis for PGD and treatment for couples with CAVD when seeking reproductive assistance.

PMID:35913788 | DOI:10.1530/REP-21-0315

J Cyst Fibros. 2022 Jul 29:S1569-1993(22)00623-3. doi: 10.1016/j.jcf.2022.07.005. Online ahead of print.

ABSTRACT

BACKGROUND: The association of certain disease processes with digital clubbing is well documented. Digital clubbing is often reversible after successful treatment of the underlying pathology, for example, after lung transplantation in patients with cystic fibrosis (CF). We examined the effect of highly effective Cystic Fibrosis Transmembrane Regulator (CFTR) modulators, defined for the purposes of this study as ivacaftor or the combination of ivacaftor, tezacaftor, and elexacaftor (ETI), on digital clubbing.

MATERIALS AND METHODS: Clubbing index was measured on plaster of Paris casts of right index fingers obtained from 15 patients with cystic fibrosis, before and after initiation of CFTR modulator therapy. Similar measurements were made on casts for 9 cystic fibrosis patients who underwent lung transplantation. Measurements were made on the most recent casts available before treatment and the first cast available at least 3 months after initiation of treatment. The Wilcoxon signed-rank text was used to detect any significant difference in the pre- and post-treatment casts for each individual.

RESULTS: A significant decrease in the clubbing index was found after both lung transplantation and treatment with highly effective CFTR modulator therapy.

CONCLUSIONS: These results add to the body of evidence demonstrating the efficacy of highly effective CFTR modulator therapy, the first agents that act directly at the dysfunctional chloride channel responsible for CF. By demonstrating that CFTR modulator therapy is capable of reversing digital clubbing, this study suggests a beneficial effect on lung pathology aside from air flow and gas transfer.

PMID:35915048 | DOI:10.1016/j.jcf.2022.07.005

BMJ Open. 2022 Aug 1;12(8):e055672. doi: 10.1136/bmjopen-2021-055672.

ABSTRACT

OBJECTIVE: To accurately estimate the global prevalence of non-tuberculous mycobacteria (NTM) in adults with non-cystic fibrosis (non-CF) bronchiectasis and to determine the proportion of NTM species and subspecies in clinical patients from 2006 to 2021.

DESIGN: Systematic review and meta-analysis using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

DATA SOURCES: Medline, Embase, Cochrane Library and Web of Science were searched for articles published between 2006 and 2021.

ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We included all the prospective or retrospective studies without language restrictions and all patients were adults (≥18 years of age) with non-CF bronchiectasis. The studies estimated the effect size of the prevalence of NTM with a sample size ≥40, and patients were registered in and after 2006.

DATA EXTRACTION AND SYNTHESIS: Two reviewers screened the titles, abstracts and full texts independently. Relevant information was extracted and curated into tables. Risk of bias was evaluated following the Cochrane Collaboration's tool. Meta-analysis was performed with software R Statistics V.3.6.3 using random effect model with 95% CI. I2 index and Q statistics were calculated to assess the heterogeneity, and mixed-effects meta-regression analyses were performed to identify the sources of heterogeneity. The proportions of NTM subspecies were examined using Shapiro-Wilk normality test in R.

RESULTS: Of all the 2014 studies yielded, 24 met the inclusion criteria. Of these, 14 were identified to be randomised controlled studies and included for an accurate estimation. The global prevalence of NTM in adults with non-CF bronchiectasis from 2006 to 2021 was estimated to be approximately 10%, with great variations primarily due to geographical location. Mycobacterium avium complex was the most common subspecies, followed by Mycobacterium simiae and Mycobacterium gordonae.

CONCLUSIONS: The prevalence of NTM in adults with non-CF bronchiectasis has been on the rise and the most common subspecies changed greatly in recent years. More cohort studies should be done in many countries and regions for future estimates.

PROSPERO REGISTRATION NUMBER: CRD42020168473.

PMID:35914904 | DOI:10.1136/bmjopen-2021-055672

Cochrane Database Syst Rev. 2022 Aug 1;8:CD008319. doi: 10.1002/14651858.CD008319.pub4.

ABSTRACT

BACKGROUND: Cystic fibrosis is a genetic disorder in which abnormal mucus in the lungs is associated with susceptibility to persistent infection. Pulmonary exacerbations are when symptoms of infection become more severe. Antibiotics are an essential part of treatment for exacerbations and inhaled antibiotics may be used alone or in conjunction with oral antibiotics for milder exacerbations or with intravenous antibiotics for more severe infections. Inhaled antibiotics do not cause the same adverse effects as intravenous antibiotics and may prove an alternative in people with poor access to their veins. This is an update of a previously published review.

OBJECTIVES: To determine if treatment of pulmonary exacerbations with inhaled antibiotics in people with cystic fibrosis improves their quality of life, reduces time off school or work, and improves their long-term lung function.

SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Group's Cystic Fibrosis Trials Register. Date of the last search: 7 March 2022. We also searched ClinicalTrials.gov, the Australia and New Zealand Clinical Trials Registry and WHO ICTRP for relevant trials. Date of last search: 3 May 2022.

SELECTION CRITERIA: Randomised controlled trials in people with cystic fibrosis with a pulmonary exacerbation in whom treatment with inhaled antibiotics was compared to placebo, standard treatment or another inhaled antibiotic for between one and four weeks.

DATA COLLECTION AND ANALYSIS: Two review authors independently selected eligible trials, assessed the risk of bias in each trial and extracted data. They assessed the certainty of the evidence using the GRADE criteria. Authors of the included trials were contacted for more information.

MAIN RESULTS: Five trials with 183 participants are included in the review. Two trials (77 participants) compared inhaled antibiotics alone to intravenous antibiotics alone and three trials (106 participants) compared a combination of inhaled and intravenous antibiotics to intravenous antibiotics alone. Trials were heterogenous in design and two were only available in abstract form. Risk of bias was difficult to assess in most trials but, for four out of five trials, we judged there to be a high risk from lack of blinding and an unclear risk with regards to randomisation. Results were not fully reported and only limited data were available for analysis. One trial was a cross-over design and we only included data from the first intervention arm. Inhaled antibiotics alone versus intravenous antibiotics alone Only one trial (18 participants) reported a perceived improvement in lifestyle (quality of life) in both groups (very low-certainty evidence). Neither trial reported on time off work or school. Both trials measured lung function, but there was no difference reported between treatment groups (very low-certainty evidence). With regards to our secondary outcomes, one trial (18 participants) reported no difference in the need for additional antibiotics and the second trial (59 participants) reported on the time to next exacerbation. In neither case was a difference between treatments identified (both very low-certainty evidence). The single trial (18 participants) measuring adverse events and sputum microbiology did not observe any in either treatment group for either outcome (very low-certainty evidence). Inhaled antibiotics plus intravenous antibiotics versus intravenous antibiotics alone Inhaled antibiotics plus intravenous antibiotics may make little or no difference to quality of life compared to intravenous antibiotics alone. None of the trials reported time off work or school. All three trials measured lung function, but found no difference between groups in forced expiratory volume in one second (two trials; 44 participants; very low-certainty evidence) or vital capacity (one trial; 62 participants). None of the trials reported on the need for additional antibiotics. Inhaled plus intravenous antibiotics may make little difference to the time to next exacerbation; however, one trial (28 participants) reported on hospital admissions and found no difference between groups. There is likely no difference between groups in adverse events (very low-certainty evidence) and one trial (62 participants) reported no difference in the emergence of antibiotic-resistant organisms (very low-certainty evidence).

AUTHORS' CONCLUSIONS: We identified only low- or very low-certainty evidence to judge the effectiveness of inhaled antibiotics for the treatment of pulmonary exacerbations in people with cystic fibrosis. The included trials were not sufficiently powered to achieve their goals. Hence, we are unable to demonstrate whether one treatment was superior to the other or not. Further research is needed to establish whether inhaled tobramycin may be used as an alternative to intravenous tobramycin for some pulmonary exacerbations.

PMID:35914011 | DOI:10.1002/14651858.CD008319.pub4

PLoS One. 2022 Aug 1;17(8):e0272355. doi: 10.1371/journal.pone.0272355. eCollection 2022.

ABSTRACT

BACKGROUND: There are few examples of interventions designed to promote physical activity (PA) in adults with Cystic fibrosis (CF). Increasing levels of habitual PA may be more feasible and result in greater compliance than conventional exercise training inventions which give little or no attention to long-term PA behaviour. Despite this there is limited research exploring perceptions of PA among adults with CF. The study aimed to understand the ecological correlates of PA in adults with CF and to involve individuals with CF, their families (where applicable) and clinicians in a formative process to inform the development of an ecological approach to PA promotion in this population.

METHODS: An iterative approach was utilised, whereby findings from earlier phases of the research informed subsequent phases. Semi-structured interviews were conducted to explore patients' perceptions of PA, devised using the PRECEDE component of the PRECEDE-PROCEED model. Followed by, focus groups to discuss the perceived barriers, facilitators and opportunities for PA participation and how this information could inform the development and delivery of a PA intervention. Separate focus groups were conducted with individuals with CF (n = 11) and their families and CF MDT members. Thematic analysis was used to construct themes.

RESULTS: Physical and mental wellbeing manifested as both barriers and facilitators of PA. CF is characterised by a progressive decline in physical function, which presents as a number of challenging symptoms and set-backs for an individual with CF. PA represents an opportunity for participants to slow the rate of this decline and manage the symptoms associated with the condition. Enjoyment was an important facilitator of PA. Exercise professionals and family reinforce PA behaviour, particularly during adolescence.

CONCLUSIONS: PA promotion should form part of routine CF care with additional exercise professional support during adolescence.

PMID:35914006 | DOI:10.1371/journal.pone.0272355

JAMA Pediatr. 2022 Aug 1. doi: 10.1001/jamapediatrics.2022.2674. Online ahead of print.

ABSTRACT

IMPORTANCE: Newborn screening (NBS) for cystic fibrosis (CF) has been universal in the US since 2010, but its association with clinical outcomes is unclear.

OBJECTIVE: To describe the real-world effectiveness of NBS programs for CF in the US on outcomes up to age 10 years.

DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective cohort study using CF Foundation Patient Registry data from January 1, 2000, to December 31, 2018. The staggered implementation of NBS programs by state was used to compare longitudinal outcomes among children in the same birth cohort born before vs after the implementation of NBS for CF in their state of birth. Participants included children with an established diagnosis of CF born between January 1, 2000, to December 31, 2018, in any of the 44 states that implemented NBS for CF between 2003 and 2010. Data were analyzed from October 5, 2020, to April 22, 2022.

EXPOSURES: Birth before vs after the implementation of NBS for CF in the state of birth.

MAIN OUTCOMES AND MEASURES: Longitudinal trajectory of height and weight percentiles from diagnosis, lung function (forced expiratory volume in 1 second, [FEV1] percent predicted) from age 6 years, and age at initial and chronic infection with Pseudomonas aeruginosa using linear mixed-effects and time-to-event models adjusting for birth cohort and potential confounders.

RESULTS: A total of 9571 participants (4713 female participants [49.2%]) were eligible for inclusion, with 4510 (47.1%) in the pre-NBS cohort. NBS was associated with higher weight and height percentiles in the first year of life (weight, 6.0; 95% CI, 3.1-8.4; height, 6.6; 95% CI, 3.8-9.3), but these differences decreased with age. There was no association between NBS and FEV1 at age 6 years, but the percent-predicted FEV1 did increase more rapidly with age in the post-NBS cohort. NBS was associated with older age at chronic P aeruginosa infection (hazard ratio, 0.69; 95% CI, 0.54-0.89) but not initial P aeruginosa infection (hazard ratio, 0.88; 95% CI, 0.77-1.01).

CONCLUSIONS AND RELEVANCE: NBS for CF in the US was associated with improved nutritional status up to age 10 years, a more rapid increase in lung function, and delayed chronic P aeruginosa infection. In the future, as highly effective modulator therapies become available for infants with CF, NBS will allow for presymptomatic initiation of these disease-modifying therapies before irreversible organ damage.

PMID:35913705 | DOI:10.1001/jamapediatrics.2022.2674