Thorax. 2022 Feb 4:thoraxjnl-2021-218461. doi: 10.1136/thoraxjnl-2021-218461. Online ahead of print.

ABSTRACT

Human papillomavirus (HPV) is the principal risk factor for cervical cancer. Transplant recipients are at a disproportionate risk of HPV complications. We conducted a single-centre, retrospective study of adult female cystic fibrosis (CF) lung transplant recipients between 2008 and 2021. We observed 12 of 34 (35.3%) with ≥1 abnormal pap smear (median age: 26.7 years). Complications included refractory anogenital warts (n=3), vulvectomy (n=2) and cervical cancer (n=4), with two deaths from metastatic disease. None with HPV morbidity was vaccinated. Lung transplant recipients had greater odds of cervical dysplasia relative to controls (OR, 3.98; 95% CI 1.17 to 11.82). CF care providers must prioritise HPV vaccination to attenuate potential future morbidity and mortality.

PMID:35121654 | DOI:10.1136/thoraxjnl-2021-218461

J Pediatr. 2022 Feb 1:S0022-3476(22)00071-3. doi: 10.1016/j.jpeds.2022.01.040. Online ahead of print.

NO ABSTRACT

PMID:35120987 | DOI:10.1016/j.jpeds.2022.01.040

J Breath Res. 2022 Feb 4. doi: 10.1088/1752-7163/ac522f. Online ahead of print.

ABSTRACT

Cystic fibrosis (CF) is characterized by chronic respiratory infections which progressively decrease lung function over time. Affected individuals experience episodes of intensified respiratory symptoms called pulmonary exacerbations (PEx) which accelerate pulmonary function decline and decrease survival. There is no standard classification for PEx, which results in treatments that are heterogeneous. Improving PEx classification and management is a significant priority for people with CF. Previous studies have shown volatile organic compounds (VOCs) in exhaled breath can be used as biomarkers because they are products of metabolic pathways dysregulated by different diseases. To provide insights on PEx classification and other clinical factors, exhaled breath was collected from subjects with CF, with some experiencing PEx and others at baseline. Exhaled breath was collected in Tedlar bags during tidal breathing for VOC analysis by solid phase microextraction coupled to gas chromatography-mass spectrometry. Statistical significance testing between quantitative and categorical clinical variables displayed percent-predicted forced expiratory volume in one second (FEV1pp) was decreased in subjects experiencing PEx. VOCs correlating with other clinical variables (body mass index, age, use of highly effective modulator therapies, and need for antibiotics) were also explored. VOCs correlating to potential confounding variables were removed and analyzed by regression for correlations with FEV1pp measurements. The VOC with the highest correlation with FEV1pp (3,7-dimethyldecane) also gave the lowest p-value when comparing subjects at baseline and during PEx. Receiver operator characteristic curves showed 3,7-dimethyldecane had a higher ability to classify PEx (area under the curve (AUC) = 0.91) relative to FEV1pp values at collection (AUC = 0.83). However, normalized ΔFEV1pp values had the highest capability to distinguish PEx (AUC = 0.93). These results show that exhaled VOCs may be a source of biomarkers for various clinical traits of CF, including PEx, that should be explored in larger sample cohorts and validation studies.

PMID:35120338 | DOI:10.1088/1752-7163/ac522f

J Assist Reprod Genet. 2022 Feb 4. doi: 10.1007/s10815-022-02417-z. Online ahead of print.

ABSTRACT

PURPOSE: Congenital bilateral absence of the vas deferens (CBAVD) is a major cause of obstructive azoospermia and male factor infertility. CBAVD is mainly caused by mutations in the genes encoding CFTR (cystic fibrosis transmembrane conductance regulator) and ADGRG2 (adhesion G protein-coupled receptor G2). This study aimed to describe CFTR and ADGRG2 variations in 46 Chinese CBAVD patients and evaluated sperm retrieval and assisted reproductive technology outcomes.

METHODS: The CFTR and ADGRG2 genes were sequenced and analyzed by whole-exome sequencing (WES), and variations were identified by Sanger sequencing. Bioinformatic analysis was performed. We retrospectively reviewed the outcomes of patients undergoing sperm retrieval surgery and intracytoplasmic sperm injection (ICSI).

RESULTS: In total, 35 of 46 (76.09%) patients carried at least one variation in CFTR, but no copy number variants or ADGRG2 variations were found. In addition to the IVS9-5 T allele, there were 27 CFTR variations, of which 4 variations were novel and predicted to be damaging by bioinformatics. Spermatozoa were successfully retrachieved in 46 patients, and 39 of the patients had their own offspring through ICSI.

CONCLUSION: There are no obvious hotspot CFTR mutations in Chinese CBAVD patients besides the IVS9-5 T allele. Therefore, WES might be the best detection method, and genetic counseling should be different from that provided to Caucasian populations. After proper counseling, all patients can undergo sperm retrieval from their epididymis or testis, and most of them can have their own children through ICSI.

PMID:35119551 | DOI:10.1007/s10815-022-02417-z

Nutr Clin Pract. 2022 Feb 3. doi: 10.1002/ncp.10842. Online ahead of print.

ABSTRACT

Cystic fibrosis (CF) is a lethal, monogenic, autosomal recessive disease with manifestations in multiple organ systems, including the lungs and gastrointestinal tract, that impact adequate nutrition. This review discusses important aspects of nutrition in adults with CF with a focus on exocrine pancreatic insufficiency, CF-related diabetes, and gastrointestinal motility, as well as how advanced lung disease, CF transmembrane conductance regulator modulators, and aging impact nutrition in CF.

PMID:35118712 | DOI:10.1002/ncp.10842

Sci Rep. 2022 Feb 3;12(1):1866. doi: 10.1038/s41598-022-05925-1.

ABSTRACT

The pathogenic variant Phe508del of the CFTR-gene is the most frequent cause of cystic fibrosis (CF). Whereas male CF-patients are infertile due to bilateral agenesis of the efferent ducts, the fertility status of male heterozygous carriers is uncertain. We aimed at demonstrating the involvement of the CFTR-ion channel during sperm capacitation and to potentially select variant-free spermatozoa in heterozygous carriers of the CFTR-variant using flow cytometry (FC). Using FC and sorting, single cell polymerase chain reaction, immuno-fluorescent staining an experimental study was performed on nine fertile semen donors and three heterozygous infertile men carrying the Phe508del gene variant. Chemical inhibition of CFTR interfered with sperm capacitation. Most viable spermatozoa of heterozygous carriers of the Phe508del variant of the CFTR-gene show immune-fluorescent CFTR. Sperm capacitation in Phe508del carriers was similar to that in healthy semen donors. Distribution of the Phe508del allele in trio data of CF-affected families corresponded to the expected recessive inheritance pattern. Infertility in Phe508del heterozygous men is unlikely to be caused by the pathogenic variant although some contribution cannot be excluded. Normal sperm capacitation in carriers of pathogenic variants of the Phe508del-gene may in part explain the high prevalence of a potentially lethal recessive disorder.

PMID:35115637 | DOI:10.1038/s41598-022-05925-1

Eur Respir J. 2022 Feb 3:2101032. doi: 10.1183/13993003.01032-2021. Online ahead of print.

ABSTRACT

Cystic fibrosis (CF) airway disease is characterised by chronic Pseudomonas aeruginosa infection. Successful eradication strategies have been hampered by a poor understanding of the mechanisms underlying conversion to chronicity. The CFTR-knockout (KO) rat harbors a progressive defect in mucociliary transport and viscosity. KO rats were infected before and after the appearance of the mucus defect, using a clinical, mucoid-isolate of P. aeruginosa embedded in agarose beads. Young KO rats that were exposed to bacteria before the development of mucociliary transport defects resolved the infection and subsequent tissue damage. However, older KO rats that were infected in the presence of hyperviscous and static mucus were unable to eradicate bacteria, but instead had bacterial persistence through 28 days post-infection that was accompanied by airway mucus occlusion and lingering inflammation. Normal rats responded to infection with increased mucociliary transport to supernormal rates, which reduced the severity of a second bacterial exposure. We therefore conclude that the aberrant mucus present in the CF airway permits persistence of P. aeruginosa in the lung.

PMID:35115338 | DOI:10.1183/13993003.01032-2021

Klin Padiatr. 2022 Feb 3. doi: 10.1055/a-1717-2178. Online ahead of print.

ABSTRACT

OBJECTIVE: Exercise-induced bronchoconstriction (EIB) occurs frequently in children and adolescents and may be a sign of insufficient asthma control. EIB is often evaluated by respiratory symptoms, spirometry, eNO measurement and methacholine testing (MCT) instead of time consuming exercise test. Aim of this study was to analyse the amount of patients for which an exercise challenge in a cold chamber (ECC) was needed for a clear EIB diagnosis, to characterize EIB phenotypes and the incidence of exercise induced laryngeal obstruction (EILO) in a large cohort of patients with EIB.

METHODS: A retrospective analysis was performed in 595 children and adolescents (mean age 12.1 years) with suspected EIB from January 2014 to December 2018. Complete data sets of skin prick test, spirometry, eNO and MCT were available from 336 patients.

RESULTS: An ECC to confirm the EIB diagnosis was performed in 125 (37.2%) of patients. Three EIB phenotypes were detected: group 1: EIB without allergic sensitization (n=159); group 2: EIB with other than house dust mite (HDM) sensitization (n=87) and group 3: EIB with HDM sensitization (n=90). MCT and eNO showed significant differences between the subgroups: An eNO>46 ppb and/or a MCT<0.1 mg was found in 23.9% vs. 50.6% vs. 57.8% in group 1-3, respectively. Significantly more patients suffered from EILO in group 1 compared to group 2 and 3 (n=13 vs. n=1).

CONCLUSION: EIB without sensitization is as often as EIB with sensitization. In patients without sensitization, EILO has to be considered as a possible cause of symptoms during exercise.

PMID:35114701 | DOI:10.1055/a-1717-2178

Respir Med. 2022 Jan 13;193:106727. doi: 10.1016/j.rmed.2021.106727. Online ahead of print.

NO ABSTRACT

PMID:35114577 | DOI:10.1016/j.rmed.2021.106727

J Med Microbiol. 2022 Feb;71(2). doi: 10.1099/jmm.0.001481.

ABSTRACT

Although anaerobic bacteria exist in abundance in cystic fibrosis (CF) airways, their role in disease progression is poorly understood. We hypothesized that the presence and relative abundance of the most prevalent, live, anaerobic bacteria in sputum of adults with CF were associated with adverse clinical outcomes. This is the first study to prospectively investigate viable anaerobic bacteria present in the sputum microbiota and their relationship with long-term outcomes in adults with CF. We performed 16S rRNA analysis using a viability quantitative PCR technique on sputum samples obtained from a prospective cohort of 70 adults with CF and collected clinical data over an 8 year follow-up period. We examined the associations of the ten most abundant obligate anaerobic bacteria present in the sputum with annual rate of FEV1 change. The presence of Porphyromonas pasteri and Prevotella nanceiensis were associated with a greater annual rate of FEV1 change; -52.3 ml yr-1 (95 % CI-87.7;-16.9), -67.9 ml yr-1 (95 % CI-115.6;-20.1), respectively. Similarly, the relative abundance of these live organisms were associated with a greater annual rate of FEV1 decline of -3.7 ml yr-1 (95 % CI: -6.1 to -1.3, P=0.003) and -5.3 ml yr-1 (95 % CI: -8.7 to -1.9, P=0.002) for each log2 increment of abundance, respectively. The presence and relative abundance of certain anaerobes in the sputum of adults with CF are associated with a greater rate of long-term lung function decline. The pathogenicity of anaerobic bacteria in the CF airways should be confirmed with further longitudinal prospective studies with a larger cohort of participants.

PMID:35113780 | DOI:10.1099/jmm.0.001481

Microb Genom. 2022 Feb;8(2). doi: 10.1099/mgen.0.000754.

ABSTRACT

Cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) are characterized by increasingly frequent acute pulmonary exacerbations that reduce life quality and length. Human airways are home to a rich polymicrobial environment, which includes members of the obligately anaerobic genus Prevotella. Despite their commonness, surprisingly little is known about the prevalence, role, genomic diversity and antimicrobial resistance (AMR) potential of Prevotella species and strains in healthy and diseased airways. Here, we used comparative genomics to develop a real-time PCR assay to permit rapid Prevotella species identification and quantification from cultures and clinical specimens. Assay specificity was validated across a panel of Prevotella and non-Prevotella species, followed by PCR screening of CF and COPD respiratory-derived cultures. Next, 35 PCR-positive isolates were subjected to whole-genome sequencing. Of eight identified Prevotella species, P. histicola, P. melaninogenica, P. nanceiensis, P. salivae and P. denticola overlapped between participant cohorts. Phylogenomic analysis revealed considerable interhost but limited intrahost diversity, suggesting patient-specific lineages in the lower airways, probably from oral cavity aspirations. Correlation of phenotypic AMR profiles with AMR genes identified excellent correlation between tetQ presence and decreased doxycycline susceptibility, and ermF presence and decreased azithromycin susceptibility and clindamycin resistance. AMR rates were higher in the CF isolates, reflecting greater antibiotic use in this cohort. All tested Prevotella isolates were tobramycin-resistant, providing a potential selection method to improve Prevotella culture retrieval rates. Our addition of 35 airway-derived Prevotella genomes to public databases will enhance ongoing efforts to unravel the role of this diverse and enigmatic genus in both diseased and healthy lungs.

PMID:35113778 | DOI:10.1099/mgen.0.000754

ACS Appl Bio Mater. 2022 Feb 3. doi: 10.1021/acsabm.1c01036. Online ahead of print.

ABSTRACT

The reliance on antibiotics and antimicrobials to treat bacterial infectious diseases is threatened by the emergence of antibiotic resistance and multi-drug-resistant organisms, thus having the potential to greatly impact human health. Thus, the discovery and development of antimicrobials capable of acting on antibiotic-resistant bacteria is a major area of significance in scientific research. Herein, we present the development of a eumelanin-inspired antimicrobial capable of killing methicillin-resistant Staphylococcus aureus (MRSA). By ligating quaternary ammonium-functionalized "arms" to a eumelanin-inspired indole with intrinsic antimicrobial activity, an antimicrobial agent with enhanced activity was prepared. This resulting antimicrobial, EIPE-1, had a minimum inhibitory concentration of 16 μg/mL (17.1 μM) against a clinical isolate of MRSA obtained from an adult cystic fibrosis patient. The biocidal activity occurred within 30 min of exposure and resulted in changes to the bacterial cell surface as visualized with a scanning electron microscope. Taken together, these studies demonstrate that EIPE-1 is effective at killing MRSA.

PMID:35113537 | DOI:10.1021/acsabm.1c01036

Pediatr Pulmonol. 2022 Feb 2. doi: 10.1002/ppul.25850. Online ahead of print.

ABSTRACT

BACKGROUND: The COVID-19 pandemic impacted many households due to shelter-in-place orders and economic hardship. People with cystic fibrosis (CF) experienced increased food insecurity compared to the general population before the pandemic, even though adequate food access is needed to maintain nutrition goals associated with improved health-related outcomes. Little is known about the impact the pandemic had on the food insecurity of people with CF and their families.

OBJECTIVE: To investigate how the COVID-19 pandemic impacted food insecurity, mental health, and self-care in people with CF.

METHODS: Adults with CF and parents/guardians of children with CF were recruited via social media to complete online questionnaires from May 2020 to February 2021. Questionnaires in English and Spanish included USDA 2-question food insecurity screening, PHQ-4 for mental health screening, and directed questions on the impact of the pandemic.

RESULTS: Of 372 respondents, 21.8% of the households experienced food insecurity during the pandemic compared to 18.8% pre-pandemic (p<0.001). More food insecure patients with CF reported weight loss (32.1% vs. 13.1%, p<0.001), worse airway clearance adherence (13.6% vs 5.8%, p<0.01), and worse medication adherence (12.4% vs 1.7%, p<0.01) compared to food secure patients. Food insecure subjects were more likely to have an abnormal mental health screen compared to food secure subjects (53.1% vs. 16.2%, p<0.001).

CONCLUSION: Food insecurity increased in the CF population during the COVID-19 pandemic. Food insecure subjects reported worse mental health and self-care during the pandemic compared to food secure subjects. This article is protected by copyright. All rights reserved.

PMID:35112507 | DOI:10.1002/ppul.25850

Front Immunol. 2022 Jan 17;12:785941. doi: 10.3389/fimmu.2021.785941. eCollection 2021.

ABSTRACT

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by beta-coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has rapidly spread across the globe starting from February 2020. It is well established that during viral infection, extracellular vesicles become delivery/presenting vectors of viral material. However, studies regarding extracellular vesicle function in COVID-19 pathology are still scanty. Here, we performed a comparative study on exosomes recovered from the plasma of either MILD or SEVERE COVID-19 patients. We show that although both types of vesicles efficiently display SARS-CoV-2 spike-derived peptides and carry immunomodulatory molecules, only those of MILD patients are capable of efficiently regulating antigen-specific CD4+ T-cell responses. Accordingly, by mass spectrometry, we show that the proteome of exosomes of MILD patients correlates with a proper functioning of the immune system, while that of SEVERE patients is associated with increased and chronic inflammation. Overall, we show that exosomes recovered from the plasma of COVID-19 patients possess SARS-CoV-2-derived protein material, have an active role in enhancing the immune response, and possess a cargo that reflects the pathological state of patients in the acute phase of the disease.

PMID:35111156 | PMC:PMC8801440 | DOI:10.3389/fimmu.2021.785941

Turk Thorac J. 2021 Nov;22(6):426-431. doi: 10.5152/TurkThoracJ.2021.20282.

ABSTRACT

OBJECTIVE: To compare class I/II cystic fibrosis transmembrane conductance regulator (CFTR) mutations to class III-V mutations with regards to cystic fibrosis disease severity markers in children.

MATERIAL AND METHODS: This study was designed as a cross-sectional study in Antalya province, located on the south coast of Turkey. The study included 38 cystic fibrosis patients aged between 0.6 and 18 years. The CFTR genotype of the patients was categorized into 2 groups based on the presence or absence of class I or class II mutations in any of the alleles. Group I comprised 8 homozygous, 8 with unknown alleles, and 8 compound heterozygous patients, and group II comprised 11 homozygous and 3 compound heterozygous patients. The groups were analyzed in respect of cystic fibrosis disease severity markers, such as spirometry, ShwachmanKulczycki score, body mass index (BMI), sweat chloride concentration, chronic Pseudomonas aeruginosa infection, annual exacerbation frequency, and severe exacerbations requiring hospitalization during the previous year.

RESULTS: In the comparison of group I and group II patients, a significant difference was observed in pancreas insufficiency (83.3% vs. 35.7%; P = .005), chronic P. aeruginosa infection (58.3% vs. 7.1%; P = .002), cough severity score (1.7 ± 1.1 vs. 0.9 ± 1.5; P = .029), number of severe exacerbations requiring hospitalization during the previous year (0.9 ± 1 vs. 0.3 ± 0.8; P = .03), and sweat chloride levels (76.7 ± 15.2 vs. 61 ± 22.3; P = .02). All these values were higher in group I patients. The mean BMI values (15.8 ± 2.2 vs. 17.6 ± 2.8; P = .03) were lower in group I patients.

CONCLUSION: There seems to be a difference between class I/II CFTR mutations and class III-V mutations on the severity of the disease in cystic fibrosis patients.

PMID:35110256 | DOI:10.5152/TurkThoracJ.2021.20282

Turk Thorac J. 2021 Jul;22(4):333-338. doi: 10.5152/TurkThoracJ.2021.20194.

ABSTRACT

OBJECTIVE: Interruption or reduction in airflow and desaturation is a theoretically expected result in bronchiectasis accompanied by excessive secretions in the airways, bronchial wall thickening, and destruction of the wall structure. The same mechanism of interruption or reduction in airflow and desaturation is valid for obstructive sleep apnea (OSA). However, data on the association of bronchiectasis with OSA are scarce. We aimed to investigate the frequency of OSA and related parameters in patients with non-cystic fibrosis bronchiectasis (NCFB).

MATERIAL AND METHODS: All 43 consecutive patients who presented to the outpatient clinic for bronchiectasis follow-up between January 1, 2018 and January 1, 2019 were included. The polysomnography (PSG) data of the 43 patients were reviewed. Groups of patients with and without OSA, as detected using PSG, were compared in terms of clinical, demographic, and polysomnographic parameters.

RESULTS: The mean age of the 43 patients was 50 ± 15 years; 28 (65.2%) were female. OSA was detected in 24 (55.8%) of 43 patients, of whom 14 (32.6%) had mild, 5 (11.6%) had moderate, and 5 (11.6%) had severe OSA. Three (7.0%) patients were REM-dependent and 7 (16.3%) were position-dependent. When evaluated using logistic regression analysis, REM percentage (16.8% vs. 11.8%, P = .03) and presence of witnessed apnea (33.3% vs. 15.7%, P = .01) were observed to be significantly higher in the patients with OSA. The age factor was found at the significance limit (P = .05).

CONCLUSION: The frequency of OSA in patients with NCFB is 55.8%. Investigating OSA using PSG is important in patients with NCFB, especially at advanced ages.

PMID:35110251 | DOI:10.5152/TurkThoracJ.2021.20194

Turk Thorac J. 2021 Jul;22(4):297-300. doi: 10.5152/TurkThoracJ.2021.20236.

ABSTRACT

OBJECTIVE: To detect the maternal and fetal problems experienced by patients with non-cystic fibrosis (non-CF) bronchiectasis during pregnancy.

MATERIAL AND METHODS: A total of 185 women aged over 18 years with medical records available, who were diagnosed as having non-CF bronchiectasis and followed in the outpatient clinic for bronchiectasis, were interviewed by phone between November 1, 2019 and December 31, 2019. Forty-seven women who accepted to participate, were able to understand and answer the survey, and had experienced at least 1 pregnancy, were included in the study, The survey questions were read and the answers were recorded. The same survey was administered to a control group of 95 women.

RESULTS: It was found that the number of patients experiencing an increase in at least 1 of the symptoms of cough, sputum production, and dyspnea during pregnancy, and the number of visits to emergency departments for respiratory conditions, were statistically significantly higher (P < .001 and P < .001, respectively), and the rate of live births was significantly lower (P = .009) in the non-CF bronchiectasis group compared with the control group. No significant difference was found between the groups in the number of miscarriages, preterm births, cesarean section, extra visits to the obstetrics department, and the presence of anomalies in the infants.

CONCLUSION: Among patients with non-CF bronchiectasis, it should be kept in mind that an increase may be seen in respiratory symptoms and the number of emergency department visits during pregnancy, and a decrease may be seen in the ratio of live births. These patients should be followed closely for these issues and measures should be taken accordingly.

PMID:35110246 | DOI:10.5152/TurkThoracJ.2021.20236

Turk Thorac J. 2021 Jul;22(4):279-283. doi: 10.5152/TurkThoracJ.2021.20121.

ABSTRACT

OBJECTIVE: Cystic fibrosis (CF) is the commonest life-limiting inherited illness in the Caucasian population but is uncommon in the Middle East, and so the genotypes and clinical course of disease in this population is not well known.

MATERIAL AND METHODS: In this retrospective observational study, we collected and reviewed the data on CF mutations, body mass index (BMI), lung function, microbiology, and the demographics in adult CF patients in the United Arab Emirates (UAE).

RESULTS: Data was reviewed for 39 adult CF patients. The median age of adult CF patients presenting to our clinic was 25 years (interquartile range (IQR) 22-31), the median BMI was 19 (IQR 17-22), and the median percentage predicted forced expiratory volume at 1 second (FEV1) was 49.5% (IQR 38.5-62.5). S549R was the commonest mutation (n = 11, 28%) followed by ∆F508 (n = 9, 23%). Only 5 (13%) out of 39 patients were heterozygote for CF mutations which reflects the high level of consanguinity in the region. Twelve (30%) patients were diagnosed after the age of 16, and in total, 19 (48%) were diagnosed after the age of 10. Thirty-two (82%) of patients are pseudomonas colonized, and 31% had 3 or more exacerbations in the last 12 months.

CONCLUSION: The CF mutation patterns in the UAE are different from western populations with low ∆F508 prevalence, with the presence of rare mutations more specific to this region and a high rate of homozygosity. Late diagnosis, high pseudomonas colonization rate, and exacerbation frequency remain a problem in this region and lead to poor long-term outcomes.

PMID:35110243 | DOI:10.5152/TurkThoracJ.2021.20121

Turk Thorac J. 2022 Jan;23(1):17-24. doi: 10.5152/TurkThoracJ.2021.21142.

ABSTRACT

OBJECTIVE: Bronchiectasis is a chronic suppurative lung disease that significantly impacts the patients' quality of life. Aim of this study is to evaluate the relationship between life of quality and patient's psychological status and bronchiectasis disease severity indexes in patients with non-Cystic Fibrosis (CF) bronchiectasis. We also aimed to investigate the validity and reliability of Turkish version of Quality-of-Life Questionnaire-Bronchiectasis (QoL-B V3.1) in Turkish adult bronchiectatic patients.

MATERIAL AND METHODS: 90 stable non-CF bronchiectatic adult patients were enrolled into this study. At baseline, dyspnea score, BMI, lung function tests, sputum cultures, number of exacerbations and hospital admissions, disease severity indexes were recorded. All of the participants underwent quality of life assessment using both QoL-B V3.1 and of Short-Form (SF)-36 questionnaires, psychological status was evaluated by using HADS (Hospital Anxiety and Depression Scale).

RESULTS: In all study participants, anxiety was diagnosed in 27/90 (30%) of patients and depression was diagnosed in 37/90 (41%) of patients. Patients with anxiety and depression had lower quality of life scores in various domains (p:0.026-p:0.001) and HADS scores negatively correlated with several quality-of-life domains (r=-0.216 - r=- 0.343). Female patients had higher risk for depression (55% vs 22%, p:0.002) and worse quality of life than males (p:0.016-p:0.038). Several life quality scores of both instruments were worse in patients with moderate-severe disease severity indexes when compared with those of mild groups. Moreover, Turkish version of newly described QoL-B V3.1 questionnaire was found to be reliable and valid instrument to evaluate the quality of life.

CONCLUSION: These results emphasize the importance of mental health and disease severity as significant determinants of the life quality in patients particularly female patients with non-CF bronchiectasis.

PMID:35110196 | DOI:10.5152/TurkThoracJ.2021.21142

J Cyst Fibros. 2022 Jan 30:S1569-1993(22)00028-5. doi: 10.1016/j.jcf.2022.01.008. Online ahead of print.

ABSTRACT

BACKGROUND: Forskolin-induced swelling of patient-derived organoids has been used to measure patient-specific CFTR function and CFTR modulator response. We present a case where CFTR function assessment in intestinal organoids was decisive for a patients' acceptance to a compassionate use program.

CASE DESCRIPTION: A 56 years old female with cystic fibrosis compound heterozygous for F508del and a rare CFTR allele (c.3717+5G>T) experienced rapid clinical deterioration. The forskolin-induced swelling assay on her rectal organoids was used to confirm that the rare mutation is a minimal residual function mutation, and that other CFTR modulators would not likely be effective. Based on these two criteria and her clinical status, she was accepted for compassionate use of elexacaftor/tezacaftor/ivacaftor and showed improvement in all clinical parameters.

CONCLUSIONS: This reports describes a first example that intestinal organoids were used to identify a previously unknown CFTR mutation as a minimal function mutation. The individual FIS-based definition of minimal residual function, response to ele/tez/iva and/or lack of response to other CFTR modulating drugs, may thus provide a tool for access to ele/tez/iva treatment for people with rare genotypes.

PMID:35110005 | DOI:10.1016/j.jcf.2022.01.008