Nontuberculous Mycobacterial Disease and Molybdenum in Colorado Watersheds.

Int J Environ Res Public Health. 2020 May 29;17(11):

Authors: M Lipner E, French J, R Bern C, Walton-Day K, Knox D, Strong M, Prevots DR, L Crooks J

Abstract
Nontuberculous mycobacteria (NTM) are environmental bacteria that may cause chronic lung disease. Environmental factors that favor NTM growth likely increase the risk of NTM exposure within specific environments. We aimed to identify water-quality constituents (Al, As, Cd, Ca, Cu, Fe, Pb, Mg, Mn, Mo, Ni, K, Se, Na, Zn, and pH) associated with NTM disease across Colorado watersheds. We conducted a geospatial, ecological study, associating data from patients with NTM disease treated at National Jewish Health and water-quality data from the Water Quality Portal. Water-quality constituents associated with disease risk were identified using generalized linear models with Poisson-distributed discrete responses. We observed a highly robust association between molybdenum (Mo) in the source water and disease risk. For every 1- unit increase in the log concentration of molybdenum in the source water, disease risk increased by 17.0%. We also observed a statistically significant association between calcium (Ca) in the source water and disease risk. The risk of NTM varied by watershed and was associated with watershed-specific water-quality constituents. These findings may inform mitigation strategies to decrease the overall risk of exposure.

PMID: 32485845 [PubMed - in process]

How to help the free market fight coronavirus.

Nature. 2020 04;580(7802):167

Authors: Burley SK

PMID: 32210376 [PubMed - indexed for MEDLINE]

An integrative review on the positive expiratory pressure (PEP)-bottle therapy for patients with pulmonary diseases.

Physiother Res Int. 2020 Jan;25(1):e1823

Authors: Liverani B, Nava S, Polastri M

Abstract
BACKGROUND AND PURPOSE: Positive expiratory pressure (PEP)-bottle device delivers a PEP within a range of 10-20 cmH2 O. PEP treatment is applied to different pathological conditions also in combination with other physiotherapeutic techniques. The primary aim of the present review was to investigate the effects of PEP-bottle therapy in patients with pulmonary diseases and, secondarily, to provide a physiological analysis of its use.
METHODS: The databases PubMed, Scopus, Web of Science, Cinahl, and Cochrane Library were searched for citations published from their inception until May 2019. Adult participants (>18 years) with pulmonary disease who underwent PEP-bottle treatment, with no restriction on gender, were included in the study. There were no restrictions about the therapeutic settings and the condition of the disease (either acute or chronic).
RESULTS: The literature review returned 97 citations. After duplicates removal, the remaining 77 articles have been screened: 66 have been assessed as not eligible at first because the abstract did not meet the inclusion criteria. Eleven articles were left after the first two steps of selection: four have been excluded after full-text reading.
CONCLUSION: PEP-bottle therapy has been proved to improve lung volume, to reduce hyperinflation, and to remove secretions. The device delivers a pressure equal to the water column only if the inner diameter of the tubing and the width of the air escape orifice are equal or greater than 8 mm, and the length of tubing ranges between 20 and 80 cm. The cost of a PEP-bottle device is significantly lower if compared with other commercially available devices having the same therapeutic purposes.

PMID: 31762162 [PubMed - indexed for MEDLINE]

Carrier frequency of CFTR variants in the non-Caucasian populations by genome aggregation database (gnomAD)-based analysis.

Ann Hum Genet. 2020 Jun 02;:

Authors: Nappo S, Mannucci L, Novelli G, Sangiuolo F, D'Apice MR, Botta A

Abstract
The complexity in the molecular diagnosis of Cystic Fibrosis (CF) also depends on the variable prevalence/incidence of the disease associated with the wide CFTR allelic heterogeneity among different populations. In fact, CF incidence in Asian and African countries is underestimated and the few patients reported so far have rare or unique CFTR pathogenic variants. To obtain insights into CF variants profile and frequency, we used the large population sequencing data in the Genome Aggregation Database (gnomAD). We selected 207 CF-causing/varying clinical consequence variants from CFTR2 database and additional 15 variants submitted to the ClinVar database. Only 14 of these variants were found in the East-Asian population, while for South-Asian and African populations we identified 43 and 52 variants, respectively, confirming the peculiarity of the CFTR allelic spectrum with only few population-specific variants. These data could be used to optimize CFTR carrier screening in non-Caucasian subjects, choosing between the full gene sequencing and cost and time-effective targeted panels.

PMID: 32484936 [PubMed - as supplied by publisher]

National Newborn Screening for cystic fibrosis in the Republic of Ireland: genetic data from the first 6.5 years.

Eur J Hum Genet. 2020 Jun 01;:

Authors: Sasaki E, Kostocenko M, Lang N, Clark T, Rogers M, Muldowney R, Walsh O, O'Grady L, Edge G, Ward A, Linnane B, Borovickova I, Barton DE, Lynch SA

Abstract
Cystic fibrosis (CF) is the most common life-limiting autosomal recessive disease in the Republic of Ireland (ROI), with a previously quoted incidence of 1 in 1353 and carrier rate of 1 in 19. The National Newborn Screening (NBS) for CF was incorporated in July 2011 in the ROI. A cut-off point of the top 1% Immunoreactive Trypsinogen (IRT) was taken as an indication for 38 CFTR variant panel to maximise identification of affected CF cases and to minimise detection of carriers. All neonates from July 2011 to Dec 2017 with an elevated IRT on NBS were tested with 38 CFTR mutation panel and included. Clinical and laboratory database were analysed. In the first 6.5 years a total of 5,053 newborns (1.16% of total births) were screened with 38 CFTR panel. 170 CF affected cases, 320 unaffected carriers, 32 CF Screening Positive Inconclusive Diagnosis (CFSPID) were identified. There was one missed diagnosis. The most common disease-causing variant was c.1521_1523delCTT (p.(Phe508del)) followed by c.1652G>A (p.(Gly551Asp)). 95 out of 170 (55%) affected newborns were homozygous for c.1521_1523delCTT (p.(Phe08del)) and 25 (15%) carried at least one copy of c.1652G>A (p.(Gly551Asp)). Hence, 70% of affected newborns were eligible for CFTR modulator treatment. The NBS programme has identified almost triple the number of affected newborn with c.1652G>A (p.(Gly551Asp)) than previously quoted figures and identified less than 50% of carriers than predicted. The revised incidence and carrier frequency of CF in the ROI is 1 in 2570 and 1 in 25, respectively.

PMID: 32483343 [PubMed - as supplied by publisher]

A longitudinal assessment of non-invasive biomarkers to diagnose and predict cystic fibrosis-associated liver disease.

J Cyst Fibros. 2020 May 30;:

Authors: Karnsakul W, Wasuwanich P, Ingviya T, Vasilescu A, Carson KA, Mogayzel PJ, Schwarz KB

Abstract
BACKGROUND & AIMS: A practical, inexpensive, and non-invasive biomarker of liver fibrosis is needed as a reliable screening test for cystic fibrosis-associated liver disease (CFLD). Studies have shown the utility of AST to Platelet Ratio Index (APRI), fibrosis index based on 4 factors (FIB-4), and gamma-glutamyl transferase (GGT) as good biomarkers for identifying CFLD. The goal of the study was to evaluate the effectiveness of APRI, FIB-4, AST/ALT ratio, platelet count, GGT, and GGT platelet ratio (GPR) in predicting CFLD development.
METHODS: Data was collected from CF Foundation Patient Registry for patients aged 3-21 years at Johns Hopkins from January 1, 2002 to December 31, 2014. Collected data included demographic characteristics, presence of splenomegaly, hepatomegaly, ascites, and variceal bleeding, AST, ALT, GGT, platelet count, and FEV1. The sensitivity and specificity of each biomarker were analyzed and reported by the area under receiver operating characteristic (AUROC) curve.
RESULTS: By the end of the study, 144 "healthy" CF, 12 CFLD, 19 CF-associated pulmonary disease (CFPD), and 4 CFLD with CFPD cases were identified. APRI scores were higher in CFLD, 0.85 versus 0.28 in "healthy" CF and 0.23 in CFPD groups (p<0.001). GPR had the highest AUROC curve at 0.91.
CONCLUSIONS: GPR, GGT, APRI score, and platelet count were potentially useful biomarkers while FIB-4 did not predict CFLD development. Cost-effectiveness studies are needed to analyze the utility of these biomarkers in clinical practice.

PMID: 32482593 [PubMed - as supplied by publisher]

Disruption of the extracellular polymeric network of Pseudomonas aeruginosa biofilms by alginate lyase enhances pathogen eradication by antibiotics.

J Cyst Fibros. 2020 May 30;:

Authors: Daboor SM, Rohde JR, Cheng Z

Abstract
BACKGROUND: Pseudomonas aeruginosa forms antibiotic-resistant biofilms that are responsible for the treatment failure or relapses of the bacterial infections in the lungs of patients with cystic fibrosis (CF). The alginate lyases that target extracellular polysaccharide alginate of P. aeruginosa biofilms are promising therapeutic candidates for treatment of P. aeruginosa biofilm infections.
METHODS: Immunofluorescent staining and thin layer chromatography were used to demonstrate the alginolytic activity of the alginate lyase enzyme (AlyP1400) purified from a marine Pseudoalteromonas bacterium. Anti-biofilm activities of AlyP1400 were tested alone or in combination with antibiotics on the biofilms of a mucoid Pseudomonas aeruginosa clinical isolate CF27 that were cultivated in 96-well plates and a flow cell.
RESULTS: We showed that AlyP1400 facilitated antibiotic activities to eliminate CF27 biofilms. The combination of AlyP1400 with antibiotics reduced the biofilm biomass and boosted bactericidal activity of antibiotics. Importantly, we demonstrated that the enzymatic activity of AlyP1400 was required for its biofilm disruption activity and its synergy with antibiotics to eradicate biofilm cells.
CONCLUSION: This work shed new light on the potential mechanisms of the therapeutic activity for the combinational use of alginate lyase and antibiotics to treat P. aeruginosa infections in CF lungs or other P. aeruginosa biofilm-related infections.

PMID: 32482592 [PubMed - as supplied by publisher]

The Role of MicroRNA in the Airway Surface Liquid Homeostasis.

Int J Mol Sci. 2020 May 28;21(11):

Authors: Mitash N, E Donovan J, Swiatecka-Urban A

Abstract
Mucociliary clearance, mediated by a coordinated function of cilia bathing in the airway surface liquid (ASL) on the surface of airway epithelium, protects the host from inhaled pathogens and is an essential component of the innate immunity. ASL is composed of the superficial mucus layer and the deeper periciliary liquid. Ion channels, transporters, and pumps coordinate the transcellular and paracellular movement of ions and water to maintain the ASL volume and mucus hydration. microRNA (miRNA) is a class of non-coding, short single-stranded RNA regulating gene expression by post-transcriptional mechanisms. miRNAs have been increasingly recognized as essential regulators of ion channels and transporters responsible for ASL homeostasis. miRNAs also influence the airway host defense. We summarize the most up-to-date information on the role of miRNAs in ASL homeostasis and host-pathogen interactions in the airway and discuss concepts for miRNA-directed therapy.

PMID: 32481719 [PubMed - in process]

Haemoptysis management in cystic fibrosis: A case report and treatment pathway.

J Clin Pharm Ther. 2020 Jun 01;:

Authors: Gavioli E, Aung CC

Abstract
WHAT IS KNOWN AND OBJECTIVE: Haemoptysis is a major complication of cystic fibrosis (CF) and is associated with pulmonary exacerbations and admission to the hospital. The US CF Pulmonary Foundation guidelines fail to reach consensus on haemoptysis treatment regarding pharmacotherapy options.
CASE SUMMARY DESCRIPTION: We describe a case in which systemic tranexamic acid was utilized to treat haemoptysis in a CF adult patient who was experiencing progressively worsening haemoptysis despite numerous bronchial artery embolization procedures.
WHAT IS NEW AND CONCLUSION: The use of antifibrinolytic agents may be of potential benefit in refractory haemoptysis episodes in adult CF patients.

PMID: 32479647 [PubMed - as supplied by publisher]

Metabolic Alkalosis and Cystic Fibrosis: A Case Report.

Ann Intern Med. 2020 Jun 02;:

Authors: Ghimire S, Yerneni H, Oyadomari TA, Sedlacek M

PMID: 32479172 [PubMed - as supplied by publisher]

Survival of Mycobacterium abscessus and Staphylococcus aureus in saline waters of the Dead Sea: implications for health tourists.

J Travel Med. 2020 Jun 01;:

Authors: Moore JE, Moore RE, Shteinberg M, Kis-Papo T, Millar BC

Abstract
M. abscessus persisted for over two weeks in Dead Sea brine and staphylococcal organisms were able to survive from three to 11 days. The uniqueness of the Dead Sea's chemical composition, particularly its extremely high salinity, eventually leads to the destruction of M. abscessus and S. aureus, including MRSA organisms.

PMID: 32478829 [PubMed - as supplied by publisher]

Phage Therapy Application to Counteract Pseudomonas aeruginosa Infection in Cystic Fibrosis Zebrafish Embryos.

J Vis Exp. 2020 May 12;(159):

Authors: Cafora M, Forti F, Briani F, Ghisotti D, Pistocchi A

Abstract
Antimicrobial resistance, a major consequence of diagnostic uncertainty and antimicrobial overprescription, is an increasingly recognized cause of severe infections, complications, and mortality worldwide with a huge impact on our society and on the health system. In particular, patients with compromised immune systems or pre-existing and chronic pathologies, such as cystic fibrosis (CF), are subjected to frequent antibiotic treatments to control the infections with the appearance and diffusion of multidrug resistant isolates. Therefore, there is an urgent need to address alternative therapies to counteract bacterial infections. Use of bacteriophages, the natural enemies of bacteria, can be a possible solution. The protocol detailed in this work describes the application of phage therapy against Pseudomonas aeruginosa infection in CF zebrafish embryos. Zebrafish embryos were infected with P. aeruginosa to demonstrate that phage therapy is effective against P. aeruginosa infections as it reduces lethality, bacterial burden and pro-inflammatory immune response in CF embryos.

PMID: 32478753 [PubMed - as supplied by publisher]

Bacterial Community Interactions During Chronic Respiratory Disease.

Front Cell Infect Microbiol. 2020;10:213

Authors: Welp AL, Bomberger JM

Abstract
Chronic respiratory diseases including chronic rhinosinusitis, otitis media, asthma, cystic fibrosis, non-CF bronchiectasis, and chronic obstructive pulmonary disease are a major public health burden. Patients suffering from chronic respiratory disease are prone to persistent, debilitating respiratory infections due to the decreased ability to clear pathogens from the respiratory tract. Such infections often develop into chronic, life-long complications that are difficult to treat with antibiotics due to the formation of recalcitrant biofilms. The microbial communities present in the upper and lower respiratory tracts change as these respiratory diseases progress, often becoming less diverse and dysbiotic, correlating with worsening patient morbidity. Those with chronic respiratory disease are commonly infected with a shared group of respiratory pathogens including Haemophilus influenzae, Streptococcus pneumoniae, Staphylococcus aureus, Pseudomonas aeruginosa, and Moraxella catarrhalis, among others. In order to understand the microbial landscape of the respiratory tract during chronic disease, we review the known inter-species interactions among these organisms and other common respiratory flora. We consider both the balance between cooperative and competitive interactions in relation to microbial community structure. By reviewing the major causes of chronic respiratory disease, we identify common features across disease states and signals that might contribute to community shifts. As microbiome shifts have been associated with respiratory disease progression, worsening morbidity, and increased mortality, these underlying community interactions likely have an impact on respiratory disease state.

PMID: 32477966 [PubMed - in process]

Circulating CRP and calprotectin to diagnose CF pulmonary exacerbations.

J Cyst Fibros. 2020 May 28;:

Authors: Jung D, Dong K, Jang J, Lam GY, Wilcox PG, Quon BS

Abstract
Cystic fibrosis (CF) pulmonary exacerbations (PEx) remain underdiagnosed by CF clinicians. Serum C-reactive protein (CRP) and calprotectin are inflammatory biomarkers that have the potential to aid in the diagnosis of PEx. 19 subjects (56 stable, 46 PEx visits) from a longitudinal study were included and the diagnostic performance of absolute and fold-change CRP and calprotectin cut-offs to discriminate stable and PEx visits was assessed. Based on Youden's index, optimal absolute and fold-change thresholds to identify PEx were 9.5 mg/L (Sn 76%, Sp 73%; AUC 0.76) and 2.2-fold (Sn 50%, Sp 96%; AUC 0.78) for CRP and 8.1 mg/L (Sn 61%, Sp 79%; AUC 0.72) and 1.3-fold (Sn 57%, Sp 88%; AUC 0.74) for calprotectin. A step-wise algorithm was able to improve diagnostic performance (Sn 80%; Sp 88%). CRP and calprotectin could discriminate stable vs. PEx visits with good performance and appear promising as diagnostic biomarkers but further validation studies are required prior to implementing these diagnostic thresholds.

PMID: 32475777 [PubMed - as supplied by publisher]

Motor dysfunction of the gut in cystic fibrosis.

Neurogastroenterol Motil. 2020 May 31;:e13883

Authors: Malagelada C, Bendezú RA, Seguí S, Vitrià J, Merino X, Nieto A, Sihuay D, Accarino A, Molero X, Azpiroz F

Abstract
BACKGROUND: Cystic fibrosis (CF) is a multisystem disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Cystic fibrosis transmembrane conductance regulator is extensively expressed in the intestine and has an important role in the regulation of the viscosity and pH of gut secretions. Several studies have reported a delay in small bowel and colonic transit times in patients with CF which have been attributed to the secretory dysfunction. Our aim was to determine whether intestinal contractility is affected in these patients.
METHODS: Consecutive patients with CF referred to our institution between 2014 and 2017 (n = 16) were prospectively investigated using automated non-invasive techniques for morpho-functional evaluation of the gut developed in our laboratory. On separate days, intraluminal images of the gut were obtained by capsule endoscopy and external images by abdominal MRI. Analysis of images (endoluminal and external) was performed with original, previously validated programs based on computer vision and machine learning techniques and compared with age- and sex-matched controls.
KEY RESULTS: Patients with CF exhibited important reduction in contractile activity and increased retention of static turbid luminal content in the small bowel by endoluminal image analysis. Morpho-volumetric analysis of MRI images found increased ileo-colonic volumes in CF. Significant correlations between abnormalities detected by intraluminal and external imaging techniques were found. The presence and severity of digestive symptoms were not related to abnormal gut function.
CONCLUSION AND INFERENCES: Impaired transit and pooling of gut contents in patients with CF is associated with impaired intestinal motility.

PMID: 32475007 [PubMed - as supplied by publisher]

Susceptibility of the Mycobacterium abscessus complex to drying: Implications for nebulizer hygiene in patients with cystic fibrosis.

Int J Mycobacteriol. 2020 Apr-Jun;9(2):173-175

Authors: Moore JE, Millar BC

Abstract
Background: Nebulizer hygiene and care is important in cystic fibrosis (CF) to minimize device contamination from bacteria, including nontuberculous mycobacteria (NTMs). Most nebulizer manufacturers recommend nebulizer drying, however there is little evidence to understand how nebulizer drying affects NTM survival.
Methods: Mycobacterium abscessus subsp. massiliense (n = 2), M. abscessus subsp. bolletii (n = 2), and M. abscessus subsp. abscessus (n = 2) were evaluated for their ability to survive simulated drying conditions associated with routine nebulizer care. Bacterial inocula (circa. 107 colony-forming units) were added to plastic and allowed to dry to completeness for 24 h, employing passive and active drying.
Results: NTM isolates of all subspecies could be recovered from all passive and active drying experiments, both in diluent and in sterile sputum, following drying (24 h). There was no combination of drying or physiology that supported NTM cell death, and there was no difference in observed survival with the three species of M. abscessus examined.
Conclusion: This study indicates that drying, either passively or actively, for 24 h at room temperature, is unable to eradicate all M. abscessus organisms from dry plastic surfaces, even in the presence of residual sputum contamination. Whilst drying may be advantageous for nebulizer performance, it should not be regarded as an absolute control for the elimination of NTM organisms. With nebulizer hygiene, NTM organisms would be able to survive on a nebulizer following drying for 24 h, which has not undergone any formal disinfection protocol. Therefore, for NTM eradication from washed nebulizers, CF patients should therefore seek an effective alternative control to drying for NTM eradication, i.e., heat disinfection in baby bottle disinfectors. CF patients and health-care professionals should not rely solely on nebulizer drying to achieve NTM eradication.

PMID: 32474539 [PubMed - as supplied by publisher]

Outcomes of pulmonary Mycobacterium abscessus infection.

Int J Mycobacteriol. 2020 Jan-Mar;9(1):48-52

Authors: Flight WG, Hough NE, Chapman SJ

Abstract
Background: Treatment of Mycobacterium abscessus pulmonary disease (PD) is challenging with frequent side effects and uncertain rates of success.
Methods: We performed a retrospective review of all patients at our center with at least one respiratory sample positive for M. abscessus between 2014 and 2019. Electronic health records were reviewed to determine factors associated with M. abscessus infection and clinical outcomes.
Results: Thirty-seven patients were identified including 24 with cystic fibrosis (CF), 10 with bronchiectasis, two with chronic obstructive PD (COPD), and one with asthma. American Thoracic Society/Infectious Diseases Society of America criteria for nontuberculous mycobacteria PD were met in 21/37 (56.8%) of cases. Evidence of Aspergillus lung disease was noted in 18 (75.0%) CF patients compared with 3 (23.1%) non-CF patients (P = 0.005). Induction therapy for M. abscessus was given to 22/37 (59.5%) patients (18/24 [75%] with CF and 4/13 [30.8%] without CF). Median duration of induction therapy was 6 weeks (range 3-12). Maintenance antibiotic therapy was prescribed to 17/22 (77.3%) of treated patients. Culture conversion was seen in 15/24 (62.5%) of CF patients compared with 3/13 (23.1%) in the non-CF group (P = 0.034). Culture conversion occurred in 10/22 (45.5%) of treated patients compared with 8/15 (53.3%) untreated patients. Three patients (8.1%) died during follow-up: one with CF and two with COPD.
Conclusions: Culture conversion following isolation of M. abscessus from respiratory samples not only is more common in CF than in patients without CF but also frequently occurs spontaneously in both groups. Targeted treatment for M. abscessus did not clearly impact rates of culture conversion.

PMID: 32474488 [PubMed - as supplied by publisher]

Oral prevalence and antifungal susceptibility of Candida species in cystic fibrosis patients.

Arch Oral Biol. 2020 May 22;116:104772

Authors: Lepesqueur LSS, Tanaka MH, Lima GMG, Chiba SM, Mota AJ, Santos SF, Koga-Ito CY

Abstract
OBJECTIVE: This study aimed at assessing the oral prevalence ofCandida species in cystic fibrosis patients and the antifungal susceptibility of the isolates.
DESIGN: One hundred patients aged 3-20 years old were included in the study and were divided into three groups: G1 (low severity disease): 25 cystic fibrosis patients with Shwachman-Kulczycki score (SK) between 100 and 71; G2 (high severity disease): 25 cystic fibrosis patients with SK score under 40; and G3 (control): 50 healthy patients age- and gender-matched to cystic fibrosis patients. Stimulated saliva samples were collected and the oral fungal concentrations were assessed. Isolates were identified by phenotypic and genotypic tests. Antifungal susceptibilities to amphotericin B, flucytosine and fluconazole were determined by CLSI methodology. Fungal counts were compared by Kruskal Wallis and Dunn's test (5%).
RESULTS: A total of 68 % of Group 1, 80 % of Group 2, and 44 % of controls yielded positive Candida cultures. Oral concentrations of fungi were significantly higher in cystic fibrosis patients in relation to the control group (p < 0.0005). No significant difference was observed between low and high severity cystic fibrosis groups (p > 0.05). C. albicans was most frequently isolated species in all groups. Higher variability of Candida species was observed in the control group. C. dubliniensis and C. tropicalis were only detected among cystic fibrosis groups. All the isolates were susceptible to flucytosine and fluconazole.
CONCLUSIONS: Patients with cystic fibrosis were more frequently colonized by Candida species and showed higher oral fungal burden. No antifungal resistant isolates were detected.

PMID: 32474212 [PubMed - as supplied by publisher]

Single Lung Transplant vs Double Lung Transplant: A Single-Center Experience With Particular Consideration for Idiopathic Pulmonary Arterial Hypertension.

Transplant Proc. 2020 May 27;:

Authors: Antończyk R, Stącel T, Urlik M, Latos M, Kręt M, Borowik D, Wajda-Pokrontka M, Zawadzki F, Tatoj Z, Przybyłowski P, Zembala M, Ochman M, Nęcki M

Abstract
BACKGROUND: Lung transplant remains the only viable treatment for certain patients with end-stage lung diseases. Such patients can become either single or double lung recipients. The 2 procedures are associated with specific risks and benefits. The aim of the study was to assess the survival of patients after lung transplant in a single center.
METHODS: The retrospective study consists of 128 lung transplant recipients. Patients underwent transplant between 2004 and 2017 because of following diseases: chronic obstructive pulmonary disease (28.2%), cystic fibrosis (26.5%), and primary pulmonary hypertension (12.3%), including idiopathic pulmonary arterial hypertension and interstitial lung diseases (33%). Patients with idiopathic pulmonary arterial hypertension were not treated with postoperative extracorporeal membrane oxygenation as left heart conditioning.
RESULTS: Regardless of underlying disease, 75% of DLT recipients and 51% of SLT recipients reached 5-year survival (P = .0066). A total of 87% of lung transplant recipients with cystic fibrosis reached 1-year survival. Among lung recipients with primary pulmonary hypertension who underwent DLT and SLT, 5-year survival was reached by 84% and 51%, respectively (P = .025). Among patients with chronic obstructive pulmonary disease, 82% of DLT recipients and 62% of SLT recipients reached 1-year survival (P = .22). Patients who received transplants because of primary pulmonary hypertension presented the worst short-term survival among all SLT recipients.
CONCLUSIONS: Patients with CF have the best overall survival among all lung transplant recipients. Double lung transplant provides statistically significantly better outcomes than single lung transplant. This observation is also present among recipients who underwent transplant because of primary pulmonary hypertension, as single lung transplant is not recommended among such patients in particular.

PMID: 32474000 [PubMed - as supplied by publisher]

Testicular pain following initiation of elexacaftor/tezacaftor/ivacaftor in males with cystic fibrosis.

J Cyst Fibros. 2020 May 26;:

Authors: Rotolo SM, Duehlmeyer S, Slack SM, Jacobs HR, Heckman B

Abstract
Elexacaftor/tezacaftor/ivacaftor (Trikafta) was approved by the Food and Drug Administration in October 2019 for treatment of cystic fibrosis (CF) in patients 12 years and older with at least one F508del mutation in the CFTR protein. There were no documented reports of testicular pain during clinical trials. In this case series, we discuss 7 males between 17 and 39 years of age who reported testicular pain or discomfort within the first two weeks of starting therapy. The precise mechanism of this side effect is unknown, but it may be related to restoration of CFTR function in the male reproductive tract. All patients experienced resolution of this side effect within a week after onset, regardless of the management, except for one. Further research is needed to determine short- and long-term impact of this drug on male fertility. Until more data is available, the authors recommend counseling patients on contraceptive options.

PMID: 32471772 [PubMed - as supplied by publisher]