Nihon Yakurigaku Zasshi. 2023;158(1):71-76. doi: 10.1254/fpj.22086.

ABSTRACT

The main function of the respiratory tract is gas exchange. Because dysfunction of gas exchange is lethal, a lot of people die of respiratory diseases every year. Many researchers are attempting to elucidate the pathophysiology of respiratory diseases and develop effective drugs using several in vitro respiratory models. Recently, respiratory organoids are widely used as human respiratory models. Respiratory organoids are self-organized three-dimensional tissue-like structures that are derived from pluripotent stem cells or tissue stem cells. Because respiratory organoids derived from a patient's stem cells carry its genetic mutation, they are widely used to recapitulate respiratory genetic diseases. It has been reported that some respiratory genetic diseases, such as cystic fibrosis, primary ciliary dyskinesia, pulmonary alveolar proteinosis, or Hermansky-Pudlak syndrome, could be recapitulated using respiratory organoids. Moreover, because respiratory organoids possess innate immune response activity, they are also used as a model for respiratory infectious diseases. It has been reported that some respiratory diseases which are caused by the infection of pathogens, such as respiratory syncytial virus, seasonal influenza viruses, human parainfluenza virus, measles virus, enterovirus, or cryptosporidium spp., could be reproduced using respiratory organoids. This review introduces the current status and future prospects of respiratory organoids in respiratory disease research.

PMID:36596495 | DOI:10.1254/fpj.22086

Can J Infect Dis Med Microbiol. 2022 Dec 24;2022:5831139. doi: 10.1155/2022/5831139. eCollection 2022.

ABSTRACT

BACKGROUND: Cystic fibrosis (CF) is an inherited recessive disorder characterized by recurrent and persistent pulmonary infections, resulting in lung function deterioration and early mortality.

METHODS: A cross-sectional study was conducted on the bacterial profile and antibiotic resistance pattern of 103 respiratory specimens from CF patients with signs of pulmonary exacerbation. Antibiotic susceptibility testing and biofilm formation of Staphylococcus aureus and Pseudomonas aeruginosa isolates were performed by the Kirby-Bauer disc diffusion method and microtiter plate assay, respectively. Molecular typing of S. aureus and P. aeruginosa isolates was carried out by spa typing and repetitive extragenic palindromic element PCR.

RESULTS: In a total of 129 isolates, the most prevalent organisms were S. aureus (55.3%) and P. aeruginosa (41.7%). Other less prevalent bacterial isolates include coagulase-negative staphylococci, Escherichia coli, klebsiella spp., Enterobacter spp., and Achromobacter xylosoxidans. The highest rate of resistance for S. aureus was observed to azithromycin and erythromycin (80%), ciprofloxacin (52.3%), clindamycin (44.6%) and tetracycline (43%). Twenty percent of S. aureus isolates were methicillin-resistant S. aureus (MRSA) and 47.6% were MDR S. aureus. For P. aeruginosa isolates the highest resistance was to cefepime (38.3%) and levofloxacin (33.3%) and 20% showed MDR phenotype.

CONCLUSION: Our study demonstrated a significant decline in the prevalence of P. aeruginosa infections in comparison to previous studies. We found S. aureus to be more prevalent in younger patients, whereas mucoid P. aeruginosa showed a shift in prevalence toward older ages. Molecular typing methods showed great diversity between isolates.

PMID:36593975 | PMC:PMC9805393 | DOI:10.1155/2022/5831139

Pediatr Pulmonol. 2023 Jan 2. doi: 10.1002/ppul.26299. Online ahead of print.

ABSTRACT

BACKGROUND: Patients with cystic fibrosis (CF) may be treated with piperacillin-tazobactam (PZT) for acute pulmonary exacerbations. Extending the infusion of PZT is one strategy to increase efficacy. Direct comparison, with respect to incidence of acute kidney injury (AKI), between these two strategies has not been evaluated in pediatric patients with CF. The primary objective of this study was to compare the incidence of AKI in pediatric CF patients receiving extended infusion (EI) PZT versus traditional infusion (TI).

METHODS: This IRB-approved, retrospective analysis included patients ages 30 days to 18 years that received PZT for at least 48 hours between 01/01/2008 and 01/01/2020. PZT was infused over thirty minutes (TI group) or four hours (EI group).

RESULTS: 204 patients were included (TI:109, EI: 95). Median age was 8 years (4-13) and 7 years (3-12) in the TI and EI groups (p=0.15). The groups did not differ significantly in their baseline characteristics. There were 12 (11%) AKIs in the TI group and 8 (8.4%) in the EI group (p=0.53). There was 1 occurrence of serum sickness in the TI group and none in the EI group. The incidence of thrombocytopenia was similar between the two groups. Median treatment duration was 8 days (5-11) and 9 days (5-13) for the TI and EI groups respectively (p=0.24).

CONCLUSIONS: There was no significant increase in AKI in pediatric patients with CF receiving PZT by EI compared to TI. EI may be utilized to optimize the pharmacokinetics of PZT in pediatric CF patients. This article is protected by copyright. All rights reserved.

PMID:36593628 | DOI:10.1002/ppul.26299

Pediatr Pulmonol. 2023 Jan 2. doi: 10.1002/ppul.26304. Online ahead of print.

ABSTRACT

BACKGROUND: Cystic fibrosis (CF)-related bone disease (CFBD) is seen in adults and can be associated with respiratory illness and malnutrition. There is limited and conflicting data regarding CFBD in pediatric CF1 . With longer life expectancy and promotion of disease prevention, pediatric CFBD demands further investigation.

METHODS: Our center initiated a quality improvement (QI) project from April 2016 to December 2018 to improve CFBD screening in patients 8 years or older, per current CF Foundation (CFF) guidelines. Our team formulated a DXA scan algorithm based upon degree of bone mineral density (BMD); shared CFBD guideline recommendations in our quarterly newsletter; and ordered scans for eligible patients at weekly review meetings. We reviewed DXA results from 141 patients after IRB approval and gathered data including co-morbidities, genetics, anthropometric measures, medication exposure, and relevant serum studies.

RESULTS: Fifty-three percent of our patients had normal BMD (n=75). Seventeen patients (12%) had a Z score ≤ -2. Patients with lower BMD also had lower mean FEV1 percent predicted (FEV1%) (p value< 0.001) as well as lower BMI % (p value= 0.001). Patients with lower BMD were overall older at time of DXA (p value= 0.016). During study duration, 13 patients who had abnormal DXA results underwent repeat DXAs after physical therapy; 11 of the 13 showed improvement in DXA results.

CONCLUSIONS: A DXA scan is a useful screening tool and can be used to identify pediatric patients who could benefit from further therapy and interventions to preserve adequate bone health and avoid further loss. QI initiatives can lead to improved screening and diagnosis and earlier intervention such as physical therapy. Further studies are needed to better understand the utility of physical therapy in children with CF. This article is protected by copyright. All rights reserved.

PMID:36593123 | DOI:10.1002/ppul.26304

In Vivo. 2023 Jan-Feb;37(1):310-319. doi: 10.21873/invivo.13081.

ABSTRACT

BACKGROUND/AIM: Lung transplantation is a life-saving procedure for patients with end-stage lung diseases. T-Cell receptor excision circle (TREC) is circular DNA produced during T-cell receptor gene rearrangement in the thymus and indicates naive T-cell migration from the thymus. Therefore, its levels represent thymic T-cell output. Post-transplant lymphocyte kinetics correlate with graft tolerance. The aim of this study was to investigate T-lymphocyte kinetics in the early recovery period after lung transplantation. For this purpose, copy numbers of TREC were determined in patients with a lung transplant. In addition, TREC copy numbers were evaluated according to age, diagnosis and the forced expiratory volume in 1 second (FEV1) of lung transplant patients.

MATERIALS AND METHODS: Peripheral blood samples were taken from patients aged 23 to 59 years who underwent lung transplantation at the Thoracic Surgery Clinic, Kartal-Koşuyolu High Specialization Educational and Research Hospital. This study included peripheral blood samples from 11 lung transplant patients (comprising four with chronic obstructive pulmonary disease, three with idiopathic pulmonary fibrosis, one with cystic fibrosis, one with silicosis and two with bronchiectasis; three females in total). Samples were taken at three different timepoints: Before transplant, and 24 hours and 7 days post transplant. TREC copy numbers were analyzed with real time reverse transcriptase-polymerase chain reaction.

RESULTS: Post-transplant TREC numbers and density values were higher compared to pre-transplant values, although these differences were statistically insignificant. TREC copy numbers were found to be significantly higher in patients younger than 45 years compared to patients older than 45 years. At 24 hours after the transplant, the average TREC copy number/peripheral blood mononuclear cells of the cases with an FEV1 value of or below 50% was found to be statistically significantly higher than that of cases with an FEV1 value above 50% (p=0.046). There was no statistically significant difference in TREC copy numbers between male and female patients or by diagnostic group.

CONCLUSION: TREC copy numbers can be evaluated as a prognostic marker for lung transplantation. There is a need for multicenter studies with more patients.

PMID:36593057 | DOI:10.21873/invivo.13081

Pediatr Pulmonol. 2023 Jan 1. doi: 10.1002/ppul.26303. Online ahead of print.

ABSTRACT

INTRODUCTION: There are no recent data on primary ciliary dyskinesia (PCD) distribution, diagnosis and treatment in Italy.

METHODS: A descriptive study based on a survey questionnaire. It consisted of three sections (patients, diagnosis and treatment), and sent to all the Italian PCD Centers.

RESULTS: questionnaires obtained from 20/22 centers in 12/20 regions showed that the total number of PCD patients treated at the participating centers was of 416. Out of all centers, 55% follow <20 patients, 2 centers have >40 patients, and 75% follow both pediatric and adults. Age at diagnosis was between 4 and 8 years in 45% of the centers, <3 years in 3 centers. Nasal nitric oxide, transmission electron microscopy and ciliary high-speed video microscopy are performed in 75, 90 and 40% of centers, respectively. Immunofluorescence is available in 5 centers. Genetic analysis is offered in 55% of the centers, and in 7 centers >50% of the patients have a known genetic profile. Patients treated at all centers receive inhaled saline solutions, corticosteroids and chest physiotherapy. Prophylactic antibiotics and mucolytics are prescribed in 95 and 50% of the centers, respectively. Pseudomonas infection is treated with oral or inhaled antibiotics.

CONCLUSIONS: Many Italian centers care for a small number of pediatric and adult patients, and diagnosis is often delayed. We found a great variability in the available diagnostic procedures, as well in the prescribed therapies. Our study will help to uniform diagnostic algorithm and share treatments protocols for PCD in Italy and allowed to set specific national goals. This article is protected by copyright. All rights reserved.

PMID:36588099 | DOI:10.1002/ppul.26303

J Cyst Fibros. 2022 Dec 28:S1569-1993(22)01434-5. doi: 10.1016/j.jcf.2022.12.014. Online ahead of print.

ABSTRACT

Patients with CF (pwCF) have high antibiotic use and an altered intestinal microbiome, known risk factors for infection with Clostridioides difficile. However, in adults with CF, C. difficile infection (CDI) is uncommon and asymptomatic colonization with C. difficile occurs frequently, for reasons that remain unclear. We investigated the rate, risk factors, and sequelae of asymptomatic C. difficile colonization in children with CF (cwCF). We identified that 32% of cwCF were colonized with C. difficile without acute gastrointestinal symptoms. Higher BMI and exposure to specific antibiotic classes (cephalosporins, fluoroquinolones, and vancomycin) were significantly associated with C. difficile colonization. No children developed symptomatic CDI in 90-days following enrollment.

PMID:36585317 | DOI:10.1016/j.jcf.2022.12.014

Turk J Pediatr. 2022;64(6):1161-1164. doi: 10.24953/turkjped.2022.342.

ABSTRACT

BACKGROUND: Cystic fibrosis (CF) is a multisystemic, autosomal recessive disease, which is caused by a mutation in the transmembrane conduction regulator protein (CFTR) gene. We present a patient who was diagnosed with CF and later diagnosed with Niemann-Pick type-A (NPA) disease, which is an autosomal recessive lysosomal lipid storage disease.

CASE: A 2-month-old Syrian refugee patient was diagnosed with CF due to a high sweat test and two homozygous CFTR-related pathogenic gene mutations in our pediatric pulmonology clinic, where she was referred due to a high immunoreactive trypsinogen (IRT) value as a result of newborn screening. As the patient had neurological symptoms and hepatosplenomegaly that could not be explained by CF in the clinical follow-up, the patient was diagnosed with NPA was made with a cherry red spot on eye examination, foam cells in the bone marrow, and low sphingomyelinase activity, in addition to CF.

CONCLUSIONS: Although CF and NP have common systems of involvement in both diseases, pathological symptoms have different origins. If a patient with CF has simultaneous neuromotor delay, other autosomal recessive diseases that may accompany it should be suspected. In studies, similar pathological pathways related to abnormal cholesterol accumulation in the cell were detected between NP type C and CF. But our case was NPA. As case reports on the coexistence of the two diseases increase, we believe that a better understanding of similar pathological pathways may lead to new therapeutic targets for both diseases.

PMID:36583901 | DOI:10.24953/turkjped.2022.342

Pulm Ther. 2022 Dec 30. doi: 10.1007/s41030-022-00210-y. Online ahead of print.

ABSTRACT

Non-tuberculous mycobacterium (NTM) infections are often clinically challenging, with lengthy antibiotic regimens that fail to resolve the infections with few good outcomes remaining. Mycobacteriophages-viruses that infect Mycobacterium hosts-show promise as therapeutic agents for NTM infections and have been used in 20 compassionate use cases. Favorable outcomes were observed in many but not all cases, although the phages show exceptional safety profiles and no evidence of phage resistance was observed, even when only a single phage was administered. Phage-specific antibodies are commonly present following intravenous administration and are often neutralizing for the phage in vitro. However, phage neutralization does not consistently correlate with poor treatment outcomes and may not be a therapeutic limitation in all patients, even when immunocompetent. Currently, the therapeutic potential of phages is substantially limited by the great variation in phage susceptibility and a relatively small repertoire of therapeutically useful phages. As many as 45% of clinical isolates can have a smooth colony morphotype, and phages that both efficiently infect and kill these strains have yet to be described. In contrast, ~ 75% of rough strains are susceptible to and killed by one or more phages and therapeutic options can be considered on a compassionate use basis. Although therapies must currently be personalized, elucidating the determinants of phage host specificity, expanding the useful phage repertoire, and identifying the key determinants of clinical outcomes will reveal their full therapeutic potential.

PMID:36583829 | DOI:10.1007/s41030-022-00210-y

Pediatr Pulmonol. 2022 Dec 29. doi: 10.1002/ppul.26296. Online ahead of print.

ABSTRACT

OBJECTIVES: Universal implementation of cystic fibrosis (CF) newborn screening (NBS) has led to the diagnostic dilemma of infants with CF screen positive, inconclusive diagnosis (CFSPID), with limited guidance regarding prognosis and standardized care. Rates of reclassification from CFSPID to CF vary and risk factors for reclassification are not well established. We investigated whether clinical characteristics are associated with risk of reclassification from CFSPID to a CF diagnosis.

METHODS: Children with a positive CF NBS were recruited from two sites in California. Retrospective, longitudinal, and cross-sectional data were collected. A subset of subjects had nasal epithelial cells collected for CFTR functional assessment. Multivariate logistic regression was used to assess the risk of reclassification.

RESULTS: A total of 112 children completed the study (CF=53, CFSPID=59). Phenotypic characteristics between groups showed differences in pancreatic insufficiency prevalence, immunoreactive trypsinogen (IRT) levels, and Pseudomonas aeruginosa (PSA) colonization. Spirometry measures were not different between groups. Nasal epithelial cells from 10 subjects showed 7-30% of wild type (WT)-CFTR function in those who reclassified and 27-67% of WT-CFTR function in those who retained the CFSPID designation. Modeling revealed that increasing sweat chloride concentration (sw[Cl- ]) and PSA colonization were independent risk factors for reclassification to CF.

CONCLUSION: Increasing sw[Cl- ] and history of PSA colonization are associated with risk of reclassification from CFSPID to CF in a population with high IRT and two CFTR variants. Close follow-up to monitor phenotypic changes remains critical in this population. The role of CFTR functional assays in this population requires further exploration. This article is protected by copyright. All rights reserved.

PMID:36582049 | DOI:10.1002/ppul.26296

Nat Commun. 2022 Dec 29;13(1):7973. doi: 10.1038/s41467-022-35553-2.

ABSTRACT

Elevated body mass index (BMI) is heritable and associated with many health conditions that impact morbidity and mortality. The study of the genetic association of BMI across a broad range of common disease conditions offers the opportunity to extend current knowledge regarding the breadth and depth of adiposity-related diseases. We identify 906 (364 novel) and 41 (6 novel) genome-wide significant loci for BMI among participants of European (N~1.1 million) and African (N~100,000) ancestry, respectively. Using a BMI genetic risk score including 2446 variants, 316 diagnoses are associated in the Million Veteran Program, with 96.5% showing increased risk. A co-morbidity network analysis reveals seven disease communities containing multiple interconnected diseases associated with BMI as well as extensive connections across communities. Mendelian randomization analysis confirms numerous phenotypes across a breadth of organ systems, including conditions of the circulatory (heart failure, ischemic heart disease, atrial fibrillation), genitourinary (chronic renal failure), respiratory (respiratory failure, asthma), musculoskeletal and dermatologic systems that are deeply interconnected within and across the disease communities. This work shows that the complex genetic architecture of BMI associates with a broad range of major health conditions, supporting the need for comprehensive approaches to prevent and treat obesity.

PMID:36581621 | PMC:PMC9798356 | DOI:10.1038/s41467-022-35553-2

BMJ Open. 2022 Sep 1;12(9):e060394. doi: 10.1136/bmjopen-2021-060394.

ABSTRACT

OBJECTIVES: Rare diseases are characterised by low incidence, often with little evidence for effective treatments. Isolated patients and specialist centres for rare diseases are increasingly connected, thanks to the internet. This scoping review aimed to identify issues facing people with a rare disease that authors report may be addressed by electronic resources (mobile applications, websites, social media platforms, telehealth and online portals).

DESIGN: Scoping review guided by the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines.

DATA SOURCES: Medline, Embase and PsycInfo were searched, supplemented by hand searches of selected journals, in July 2021.

ELIGIBILITY CRITERIA: Peer-reviewed literature in English was searched using terms for rare disease (incidence <1:2000), electronic modalities (eg, mobile phone) and patient support terms. No date limit was set. Conference abstracts were included.

DATA EXTRACTION AND SYNTHESIS: Data extracted: rare disease/group of diseases, name of the e-resource, need identified in the patient cohort, features of the e-resource, any other findings or observations of interest. From this, a framework was developed synthesising features across diseases and resources.

RESULTS: Seventy-two papers were found (from 383). Fifty-six electronic resources were described in 64 papers, while 12 papers were exploratory studies. Cystic fibrosis (n=28) was the most frequently addressed, followed by haemophilia (n=16).Four domains and 23 subdomains of needs were extracted from the papers. The domains of needs were: support for self-management, access to high-quality information, access to appropriate specialist services, and social support. Subdomains are sometimes related to needs of individual rare diseases (eg, social isolation due to infection risk in people with cystic fibrosis). Fifteen electronic resources were identified that supported parents of children with rare disorders.

CONCLUSIONS: While it can be argued that rare diseases, per se, may be no less distressing or onerous to care for than a high prevalence disease, rare diseases have unique features: the lengthy odyssey to find a diagnosis, then appropriate specialists, the lack of evidence around effective treatments, guidelines or access to knowledgeable general health service providers. Designers of electronic resources are urged to consult key stakeholders to enhance the effectiveness and usability of resources for people with a rare disease.

PMID:36581982 | DOI:10.1136/bmjopen-2021-060394

J Cyst Fibros. 2022 Dec 27:S1569-1993(22)01429-1. doi: 10.1016/j.jcf.2022.12.009. Online ahead of print.

ABSTRACT

Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was shown to be safe and efficacious in people with cystic fibrosis (CF) with ≥ 1 F508del-CFTR allele in Phase 3 clinical trials. ELX/TEZ/IVA treatment led to improved lung function, with increases in percent predicted forced expiratory volume in 1 second (ppFEV1) and Cystic Fibrosis Questionnaire-Revised respiratory domain score. Here, we evaluated the impact of ELX/TEZ/IVA on the rate of lung function decline over time by comparing changes in ppFEV1 in participants from the Phase 3 trials with a matched group of people with CF from the US Cystic Fibrosis Foundation Patient Registry not eligible for cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy. Participants treated with ELX/TEZ/IVA had on average no loss of pulmonary function over a 2-year period (mean annualized rate of change in ppFEV1, +0.39 percentage points [95% CI, -0.06 to 0.85]) compared with a 1.92 percentage point annual decline (95% CI, -2.16 to -1.69) in ppFEV1 in untreated controls. ELX/TEZ/IVA is the first CFTR modulator therapy shown to halt lung function decline over an extended time period.

PMID:36581485 | DOI:10.1016/j.jcf.2022.12.009

J Cyst Fibros. 2022 Dec 27:S1569-1993(22)01426-6. doi: 10.1016/j.jcf.2022.12.006. Online ahead of print.

ABSTRACT

BACKGROUND: Study 661-110 (EXTEND) is a phase 3, open-label, three-part rollover study designed to assess the long-term safety and efficacy of tezacaftor/ivacaftor (TEZ/IVA) in participants aged ≥12 years homozygous for F508del (F/F) or heterozygous for F508del and a residual function mutation (F/RF). TEZ/IVA was shown to be safe and efficacious for up to 120 weeks in Part A. Here we report results from Part B, which evaluated safety and efficacy for an additional 96 weeks.

METHODS: Part B enrolled participants aged ≥12 years with CF and F/F or F/RF genotypes who completed TEZ/IVA treatment in either Study 661-110 Part A, Study 661-112 (F/F), or Study 661-114 (F/F). Participants received TEZ 100 mg/IVA 150 mg fixed-dose combination once daily (morning) and IVA 150 mg once daily (evening) for 96 weeks. Safety endpoints included adverse events (AEs) and serum liver function tests. Efficacy endpoints included absolute change from baseline in percent predicted forced expiratory volume in 1 second (ppFEV1) and pulmonary exacerbation (PEx) rate.

RESULTS: 464 participants were enrolled from Part A (n=377) and other eligible studies (n=87); 463 received ≥1 dose of TEZ/IVA. Overall, 92.2% had ≥1 AE, 0.9% had AEs leading to treatment discontinuation, and 29.4% reported serious AEs. The most common AEs, which were generally consistent with common manifestations of CF, included infective PEx of CF, cough, nasopharyngitis, hemoptysis, and headache. Lung function was maintained over 96 weeks in both genotype groups. PEx rates per year were comparable with Part A.

CONCLUSIONS: TEZ/IVA was generally safe and well tolerated over a further 96 weeks; safety data were consistent with Part A. Improvements in ppFEV1 and PEx rates were maintained for an additional 96 weeks in Part B.

PMID:36581484 | DOI:10.1016/j.jcf.2022.12.006

Paediatr Respir Rev. 2022 Dec 5:S1526-0542(22)00086-0. doi: 10.1016/j.prrv.2022.11.005. Online ahead of print.

ABSTRACT

Cystic fibrosis-related diabetes (CFRD) is a common complication of CF that increases in incidence as patients age. Poor glycemic control has been shown to negatively impact lung function and weight, resulting in higher risk of recurrent pulmonary exacerbations. With the advent of highly effective modulator therapies (HEMT), patients with CF are living longer and healthier lives. Consequently, CFRD and its microvascular complications are rising in prominence, becoming one of the most urgent clinical concerns. As HEMT were developed with the primary focus of improving pulmonary outcomes, it is not clear from the original phase III studies what the short- or long-term benefits of modulators might be on CFRD development and trajectory. In this review, we will examine the pathophysiology of CFRD, summarize and synthesize the available evidence of HEMT impact on CFRD and describe the emerging research needs in this field.

PMID:36581478 | DOI:10.1016/j.prrv.2022.11.005

J Allergy Clin Immunol Pract. 2022 Dec 26:S2213-2198(22)01325-3. doi: 10.1016/j.jaip.2022.12.012. Online ahead of print.

ABSTRACT

BACKGROUND: An unmet clinical need exists in the management of treatment-refractory allergic bronchopulmonary aspergillosis (ABPA). Omalizumab has shown promising effects in case series and cohort studies; however, evidence to support its routine clinical use is lacking.

OBJECTIVE: The aim of this systematic review and meta-analysis was to evaluate the clinical effectiveness and safety of omalizumab in patients with ABPA.

METHODS: A systematic search across standard databases was conducted using specific keywords until May 13, 2021. A meta-analysis was performed to compare the effectiveness (exacerbations, oral corticosteroid [OCS] use, lung function, patient-reported asthma control) and safety of pre- and post- omalizumab treatment. Subgroup analyses were performed for treatment duration and underlying disease.

RESULTS: In total, 49 studies (n=267) were included in the qualitative synthesis and 14 case series (n=186) in the quantitative meta-analysis. Omalizumab treatment significantly reduced the annualized exacerbation rate versus pre-treatment (mean difference [MD]: -2.09 [-3.07; -1.11], P<0.01). There was a reduction in the OCS use (risk difference [RD]: 0.65 [0.46;0.84], P<0.01), an increase in termination of OCS use (RD: 0.53 [0.24;0.82], P<0.01), and a reduction in OCS dose (mg/day) (MD: -14.62 [-19.86; -9.39]; P<0.01) in ABPA patients receiving omalizumab. Omalizumab improved forced expiratory volume in 1 second (FEV1) % predicted by 11.9% (8.2; 15.6, P<0.01) and asthma control, and was well tolerated.

CONCLUSION: Omalizumab treatment reduced exacerbations and OCS use and improved lung function and asthma control in patients with ABPA and was well tolerated. The results highlight the potential role of omalizumab in the treatment of ABPA.

PMID:36581073 | DOI:10.1016/j.jaip.2022.12.012

EBioMedicine. 2022 Dec 27;87:104428. doi: 10.1016/j.ebiom.2022.104428. Online ahead of print.

NO ABSTRACT

PMID:36580850 | DOI:10.1016/j.ebiom.2022.104428

J Magn Reson Imaging. 2022 Dec 29. doi: 10.1002/jmri.28584. Online ahead of print.

NO ABSTRACT

PMID:36579435 | DOI:10.1002/jmri.28584

Proc (Bayl Univ Med Cent). 2022 Aug 18;36(1):118-120. doi: 10.1080/08998280.2022.2111645. eCollection 2023.

ABSTRACT

Central diabetes insipidus (DI) is an uncommon condition caused by reduced or lack of vasopressin secretion from the posterior pituitary gland, typically caused by gland destruction. Several other causes for central DI have also been proposed. Here we present a case of transient central DI after discontinuation of vasopressin used for septic shock without evidence of overt pituitary damage in a cystic fibrosis patient. The serum sodium concentration peaked at 137 mmol/L in the setting of polyuria within 3 days of vasopressin discontinuation without other identified alternative etiologies. Sodium levels and urine output trended down dramatically with desmopressin administration.

PMID:36578627 | PMC:PMC9762782 | DOI:10.1080/08998280.2022.2111645

Respirol Case Rep. 2022 Dec 22;11(1):e01077. doi: 10.1002/rcr2.1077. eCollection 2023 Jan.

ABSTRACT

As functional respiratory impairment following COVID-19 infection (COVID-19) is increasingly reported in adult, data regarding children especially with pre-existing chronic respiratory disease (PCRD) remain scarce. We retrospectively assessed clinical presentation, duration of symptoms related to COVID-19 from paediatric patients with PCRD and compared their pre/post COVID-19-I spirometry values. Data from 12 patients were analysed. Timing between COVID-19 diagnosis and subsequent functional evaluation ranged from 26 to 209 days (mean 77). The PCRD in these patients included asthma, cystic fibrosis, bronchiolitis obliterans and bronchomalacia. During COVID-19, all clinical presentations were mild. One patient displayed persistent post-COVID-19 symptoms for 8 weeks after infection. Two patients presented significant deterioration of post-COVID-19 spirometric values with a return to pre-COVID-19 values in subsequent measures. We concluded that children with PCRD are not at increased risk for severe COVID disease and that most of them have no or only transient pulmonary functional impairment 1 to 7 months after COVID-19.

PMID:36578269 | PMC:PMC9780698 | DOI:10.1002/rcr2.1077