Is there a role for lung or bronchial biopsies for the diagnosis of mycobacterial pulmonary disease in patients with bronchiectasis?

Background: Workup of bronchiectasis patients mandates microbiological characterization often being sought via Bronchoscopy. However, whether to perform bronchial or lung biopsies, is unknown, especially for the diagnosis of NTM pulmonary disease. We aimed to assess the current practice and yield of the different bronchoscopic procedures in this setting. Methods: Data from an adult cohort with bronchiectasis referred for bronchoscopy for microbiologic sampling was reviewed, including demographics, etiology, imaging and results of the different bronchoscopic procedures performed. Results: 127 subjects were analyzed (mean age 61, 56% female). BAL culture was positive in 44%. Frequent pathogens were Hemophilus Influenza (20%), pseudomonas aeruginosa (8%) and Staphylococcus aureus (7%). NTM and tuberculosis were found in 6% and 1.5% respectively. BAL cytology was sent in 125 procedures, EBB was performed in 51 patients (40%) and TBLB in 38 patients (30%). BAL cytology and both EBB and TBB (including tissue cultures) had no benefit over BAL with respect to microbiological diagnosis, including identification of mycobacterial disease. Conclusions: In adult subjects with Non-CF bronchiectasis requiring bronchoscopy for microbiological characterization, BAL cytology and lung tissue biopsies were frequently performed but were of minimal additional benefit over BAL culture (including for mycobacterial pulmonary disease), and are most likely futile.

Residual symptoms, lung function, and imaging findings in patients recovering from SARS-CoV-2 infection.

Symptoms following acute COVID-19 infection are common, but their relationship to initial COVID-19 severity is unclear. We hypothesize that residual symptoms are related to disease severity, and severe acute COVID-19 infection is more likely to cause residual pulmonary damage. This study aims to evaluate symptoms, lung function, and abnormal imaging within 3 months following COVID-19 infection, and to determine whether they are related to initial disease severity. A cross-sectional study was carried out at a designated post-COVID clinic in Hadassah Medical Center, Jerusalem, Israel. Patients with PCR-confirmed SARS-CoV-2 infection were evaluated within 12 weeks following infection and included both admitted and non-admitted subjects. All study participants underwent assessment of symptoms, quality of life (SGRQ), pulmonary function tests, and imaging. A total of 208 patients (age 49.3 ± 16 years) were included in the study. Initial disease severity was mild in 86, moderate in 49, and severe in 73 patients. At the time of follow-up, there were no differences in frequency of residual symptoms or in SGRQ score between groups. Patients with severe COVID-19 were more likely to have residual dyspnea (p = 0.04), lower oxygen saturation (p < 0.01), lower FVC and TLC (p < 0.001, p = 0.03 respectively), abnormal CXR (p < 0.01), and abnormal CT scan (p < 0.01) compared to other groups.Frequency of symptoms and impairment of quality of life at 12 week follow-up are common and are not related to severity of initial COVID-19 disease. In contrast, reduced lung function and abnormal pulmonary imaging are more common in patients with more severe acute COVID-19 infection.

Characteristics of Sarcoidosis in Patients with Previous Malignancy: Causality or Coincidence?

BACKGROUND: The association between sarcoidosis and malignancy is poorly defined. Sarcoidosis can precede, be diagnosed concurrently with, or follow malignancy. OBJECTIVES: We describe the clinical and radiological features of patients with sarcoidosis following malignancy to determine whether this association is causal or coincidental. METHODS: We performed a search for all patients with confirmed sarcoidosis following malignancy in our institution during 2001-2015. Clinical and radiological features, bronchoscopic findings, bronchoalveolar lavage cell counts, and pulmonary function tests (PFTs) were reviewed to evaluate patterns of disease involvement. Details of the histological type of cancer, staging, treatment, and follow-up were reviewed. RESULTS: Twenty-nine patients were identified. The most prevalent malignancies were breast cancer and lymphoma (24% each). Based on the incidence of these malignancies, we estimated the incidence of sarcoidosis was 175 times higher after lymphoma and 38 times higher after breast cancer as compared to the general population. Most patients had early stage cancer (stage I, II) (75%), and only 2 patients (7%) had recurrence of their malignancy after diagnosis of sarcoidosis. Sarcoidosis was diagnosed within 5 years of malignancy in over half the patients, 76% were asymptomatic and 69% had normal PFTs. Mediastinal lymphadenopathy was present in 81% of cases, hilar lymphadenopathy in 67%, and pulmonary parenchymal involvement in 41%. Fifty percent of patients had received Adriamycin, 38% cyclophosphamide, and 33% vincristine. CONCLUSIONS: Sarcoidosis following malignancy is indistinguishable from "idiopathic" sarcoidosis, although it is frequently asymptomatic. The high frequency of sarcoidosis after specific cancers but not others, suggests a causative association between malignancy and development of sarcoidosis.

A homozygous nonsense CEP250 mutation combined with a heterozygous nonsense C2orf71 mutation is associated with atypical Usher syndrome.

BACKGROUND: Usher syndrome (USH) is a heterogeneous group of inherited retinitis pigmentosa (RP) and sensorineural hearing loss (SNHL) caused by mutations in at least 12 genes. Our aim is to identify additional USH-related genes. METHODS: Clinical examination included visual acuity test, funduscopy and electroretinography. Genetic analysis included homozygosity mapping and whole exome sequencing (WES). RESULTS: A combination of homozygosity mapping and WES in a large consanguineous family of Iranian Jewish origin revealed nonsense mutations in two ciliary genes: c.3289C>T (p.Q1097*) in C2orf71 and c.3463C>T (p.R1155*) in centrosome-associated protein CEP250 (C-Nap1). The latter has not been associated with any inherited disease and the c.3463C>T mutation was absent in control chromosomes. Patients who were double homozygotes had SNHL accompanied by early-onset and severe RP, while patients who were homozygous for the CEP250 mutation and carried a single mutant C2orf71 allele had SNHL with mild retinal degeneration. No ciliary structural abnormalities in the respiratory system were evident by electron microscopy analysis. CEP250 expression analysis of the mutant allele revealed the generation of a truncated protein lacking the NEK2-phosphorylation region. CONCLUSIONS: A homozygous nonsense CEP250 mutation, in combination with a heterozygous C2orf71 nonsense mutation, causes an atypical form of USH, characterised by early-onset SNHL and a relatively mild RP. The severe retinal involvement in the double homozygotes indicates an additive effect caused by nonsense mutations in genes encoding ciliary proteins.

Mutations in ARL2BP, encoding ADP-ribosylation-factor-like 2 binding protein, cause autosomal-recessive retinitis pigmentosa.

Retinitis pigmentosa (RP) is a genetically heterogeneous retinal degeneration characterized by photoreceptor death, which results in visual failure. Here, we used a combination of homozygosity mapping and exome sequencing to identify mutations in ARL2BP, which encodes an effector protein of the small GTPases ARL2 and ARL3, as causative for autosomal-recessive RP (RP66). In a family affected by RP and situs inversus, a homozygous, splice-acceptor mutation, c.101-1G>C, which alters pre-mRNA splicing of ARLBP2 in blood RNA, was identified. In another family, a homozygous c.134T>G (p.Met45Arg) mutation was identified. In the mouse retina, ARL2BP localized to the basal body and cilium-associated centriole of photoreceptors and the periciliary extension of the inner segment. Depletion of ARL2BP caused cilia shortening. Moreover, depletion of ARL2, but not ARL3, caused displacement of ARL2BP from the basal body, suggesting that ARL2 is vital for recruiting or anchoring ARL2BP at the base of the cilium. This hypothesis is supported by the finding that the p.Met45Arg amino acid substitution reduced binding to ARL2 and caused the loss of ARL2BP localization at the basal body in ciliated nasal epithelial cells. These data demonstrate a role for ARL2BP and ARL2 in primary cilia function and that this role is essential for normal photoreceptor maintenance and function.

Randomized controlled crossover trial of a new oscillatory device as add-on therapy for COPD.

A new oscillatory device administers predetermined pressure oscillation sequences into the chest cavity over inhaled/exhaled air streams at low positive pressure. We assessed device safety and effect on 6MW performance, pulmonary function, and health-related quality-of-life (HRQOL) in moderate-to-very severe COPD in a randomized, double-blind, controlled, crossover study. Outcomes with an oscillatory device (Pulsehaler(TM), Respinova Ltd, Herzliya, Israel) and a "muted" sham device (control) of identical appearance that delivered continuous positive air pressure were compared in two groups receiving opposite treatment sequences: 2-week oscillatory device/control, 2-week washout, 2-week control/oscillatory device, 2-week washout. The clinical trial was registered ( www.clinicaltrials.gov , NCT00821418) and approved by the Hadassah-Hebrew University Medical Center Institutional Review Board (08-608). All participants signed informed consent; 22 patients completed the study with no marked differences in COPD exacerbations or side effects. A total of 91% of patients treated with the oscillatory device had a clinically significant improvement (increase >40 m) in 6MW performance. The 6MW distance with the oscillatory device increased significantly after 1 week of treatment (51.6 ± 7.6 m, +13.5 ± 2.3%, p < 0.001), and more after 2 weeks (61.8 ± 9.0 m, 16.3 ± 2.7%, p < 0.001). This increase with the oscillatory device was significantly greater (p < 0.001) than the 15.4 ± 10.4 m increase (4.2 ± 2.6%, NS) with control. FVC and inspiratory capacity (IC) improved significantly (p = 0.03 for each) with the oscillatory device but not with control. HRQL improved markedly (≥1 point) for dyspnea and mastery with the oscillatory device (p = 0.02) but not control. Treatment with a new oscillatory device appears to be safe, and to improve 6MW performance, pulmonary function, and HRQL in COPD. Further evaluation is warranted.

National asthma observational survey of severe asthmatics in Israel: the no-air study.

BACKGROUND: Asthma is considered a global public health issue requiring a significant medical expenditure as a result of its high prevalence and the low rate of disease control. OBJECTIVE: This is the first nationwide survey of severe asthma patients carried out in Israel. In this study we aimed to assess health resources utilization, compliance with treatment and disease-control in a subgroup of patients with severe asthma in Israel. MATERIAL AND METHOD: One hundred and twenty-three patients with a diagnosis of asthma for more then one year, as well as a hospitalization during the last 12 months due to asthma exacerbation or maintenance systemic steroids therapy, were included in this non-interventional observational study. RESULTS: Asthma was uncontrolled in 43.9%, partly controlled in 50.4% and well controlled in only 5.7%. The majority of the patients (83%) were compliant with drug treatment. CONCLUSION: The fact that 83% of the asthma patients included in this study were compliant with their asthma therapy was not manifested in asthma control. Therefore concrete tools are required for achieving and maintaining asthma control, especially in the treatment of the most severe asthmatic patients.

Disseminated Mycobacterium kansasii infection with pulmonary alveolar proteinosis in a patient with chronic myelogenous leukemia.

A 64-year-old woman with chronic myelogenous leukemia (CML) was admitted due to prolonged fever and lung infiltrates. An open lung biopsy was required to make the diagnosis of pulmonary alveolar proteinosis (PAP) and infection with Mycobacterium kansasii. She was treated successfully with combined antimycobacterial therapy for 14 months. However, the leukemia progressed and the patient developed recurrent bilateral lung infiltrates. Blood and bronchoalveolar fluid cultures yielded growth of Acinetobacter. She died shortly thereafter due to septic shock. The relationship between M. kansasii infection, PAP, and abnormal host defense in CML is discussed.

Exacerbation of pulmonary sarcoidosis after liver transplantation.

Patients with hepatic sarcoidosis rarely require orthotopic liver transplantation (OLT). Progression of granulomatous activity involving other organs after OLT has rarely been described. We describe a 32-year-old woman who underwent liver transplantation for sarcoidosis-associated end-stage liver disease. She presented 4 years later with shortness of breath, hilar lymphadenopathy, and interstitial lung abnormalities. Liver functions were normal. Open lung biopsy results revealed granulomata compatible with sarcoidosis. The patient made a complete recovery after corticosteroid treatment. To the best of our knowledge, this is a first description of severe exacerbation of pulmonary sarcoidosis in an immunosuppressed patient who underwent liver transplantation for sarcoidosis-associated liver disease.