Israel Medical Association Journal

Background: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommends a ratio of forced expiratory volume in one second (FEV1) to forced vital capacity (FVC) of less than 70% (FEV1/FVC < 0.7) after bronchodilators as the criteria for obstruction. However, because the FEV1/FVC ratio decreases with age, using a fixed ratio may lead to overdiagnosis of obstruction in the geriatric population. Using the lower limit of normal (LLN) as threshold for obstruction has been suggested.

Objectives: To determine the rate of overdiagnosis using the GOLD criteria compared to LLN in patients aged 60 and older. To find a better threshold with a minimal rate of over- and underdiagnosis.

Methods: The study population included adults aged 60 years and older who performed pulmonary function test (PFT) at Shaare Zedek Medical Center between 2014 and 2019 with results of FEV1/FVC < 0.7.

Results: We included 430 patients aged 60 years and older, 273 males (63.5%) and 157 females (36.5%). Mean age was 72 ± 8 years. Overdiagnosis was found in 35.6% of patients (95% confidence interval 31.1–40.3%) by using the GOLD criteria compared to the LLN. Overdiagnosis was reduced to 6.4% with the 0.65 threshold. The ideal point of the FEV1/FVC ratio where overdiagnosis and underdiagnosis were at their lowest rates was 0.638.

Conclusions: Use of the GOLD criteria for airflow obstruction may be associated with an overdiagnosis of more than 35% in patients older than 60 years. Lowering the FEV1/FVC ratio to < 0.65 might be more accurate in this population.

Background: Lung transplantation (LT) is a viable option for end-stage chronic obstructive pulmonary disease (COPD) patients when conventional treatments fail. However, sex disparities in mortality outcomes among COPD patients awaiting LT remain understudied. LT waiting lists are generally shorter in Western countries compared to Israel.

Objectives: To evaluate sex-specific differences in mortality and co-morbidities among COPD patients awaiting lung transplantation, to identify key risk factors influencing survival.

Methods: We assessed associations between sex, co-morbidities, exacerbations, and mortality using Cox regression models, adjusting for confounders. Survival curves for lung transplant candidates were stratified by sex using Fine and Gray models.

Results: We identified 385 COPD patients listed for LT at Rabin Medical Center. Females exhibited higher rates of asthma (P = 0.008), anxiety (P = 0.005), and depression (P = 0.002); males were more frequently diagnosed with ischemic heart disease (26.5% vs. 10.83%, P = 0.001) and had a higher lung transplant rate (24.9% vs. 15%, P = 0.029). Multivariate analysis revealed that female sex (hazard ratio [HR] 1.55, 95% confidence interval [95%CI] 1.06–2.29, P = 0.025), older age (HR 1.02, 95%CI 1.002–1.054, P = 0.035), ischemic heart disease (HR 1.69, 95%CI 1.12–2.48, P = 0.011), and depression (HR 1.81, 95%CI 1.15–2.83, P < 0.01) were significantly associated with increased mortality. Females showed higher 1-year mortality rates than males (40.3% vs. 29.8%, P < 0.001).

Conclusions: Female sex is a significant risk factor for increased mortality among COPD patients awaiting LT, likely due to a higher burden of co-morbidities.

Background: Lung transplantation is an advanced medical therapy reserved for patients with end-stage lung disease. Relative to other solid organ transplants, lung transplantation in children is infrequently performed. The most common etiologies for pediatric lung transplantation worldwide are cystic fibrosis, pulmonary hypertension, and children’s interstitial lung disease.

Objectives: To describe our experience in pediatric lung transplants at Israel's largest transplant center.

Methods: We performed a retrospective review of all pediatric lung transplantations conducted in our center since 1997. We recorded demographic characteristics, indication for transplantation, clinical and laboratory parameters, post-transplant complications, and survival rates.

Results: Of 965 lung transplants, 29 (3.0%) were pediatric patients who underwent lung or heart-lung transplants for end-stage lung disease. Age at transplantation ranged from 2 to 18 years, with a median of 14.0 years (IQR 11–15). Primary etiologies for transplantation were cystic fibrosis (44%), pulmonary hypertension (17%), and children’s interstitial lung disease (10%). Survival at 1, 5, 10, and 15 years post-transplant were 90%, 65%, 55%, and 20%, respectively, which is consistent with data reported by pediatric lung transplantation registries. The primary cause of mortality post-transplant was chronic lung allograft dysfunction. Four patients (13.8%) underwent re-transplant. There was no association between survival and transplant indication, nor between survival and type of procedure (lung vs. heart-lung transplant).

Conclusions: The short- and long-term outcomes from our program are consistent with published registry data. These outcomes may reflect the benefits of a centralized pediatric lung transplant program, supported by a multidisciplinary team trained in high-capacity international centers.

Background: Lung cancer is a major cause of death worldwide. Accurate diagnosis and staging are essential for effective treatment. Mediastinal lymph node involvement determines the disease stage and influences treatment decisions, especially with new biological and immunotherapy options. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is the main minimally invasive procedure for evaluating mediastinal and hilar adenopathy. It offers high sensitivity, specificity, and fewer complications than mediastinoscopy or video-assisted thoracic surgery. It also retrieves crucial molecular markers for guiding therapeutic decisions in non-small cell lung cancer.

Objectives: To evaluate the diagnostic yield of EBUS-TBNA in patients with mediastinal lymphadenopathy.

Methods: This retrospective study included patients who underwent bronchoscopy with EBUS and had lymph node malignancy between 2018 and 2023. Crossmatching was conducted by pathology and genomic study results. No informed consent was required as the study was based on the hospital database.

Results Next generation sequencing was performed on 57 specimens (83%) collected via EBUS from patients with primary non-small cell lung cancer. However, 12 of the specimens (17%) were insufficient for pathological analysis. Among these, 7 (58%) were from adenocarcinomas and 5 (42%) were from squamous cell carcinoma patients.

Conclusions: The utilization of EBUS-TBNA is an effective tool for obtaining genetically profiled diagnoses by minimally invasive means. As more genetic mutations are discovered, we expect that multigene mutation analysis will gain importance in tailoring individualized treatment plans.

Cerebral arterial air embolism (CAAE) is a rare, but often fatal, complication of interventional bronchoscopy. Despite its rarity, a high index of suspicion can facilitate early diagnosis and prompt treatment. Standard of care treatment for CAAE is hyperbaric oxygen therapy, despite limited definitive data supporting its efficacy, given the conceptual potential for reversibility of neurological impairment. We describe five cases from our institution, and review the clinical presentation, pathophysiology, diagnosis, and management of suspected CAAE. Based on published case reports involving transbronchial lung biopsies (TBLB), standard of care treatment for CAAE secondary to TBLB is hyperbaric oxygen therapy, although its efficacy in this context has not been unambiguously validated in clinical practice.

We summarized the role of lung ultrasound for diagnosing and monitoring various pediatric respiratory diseases. We began with an overview of the basics of the tool, followed by describing its use in conditions such as pneumonia, pleural effusion, bronchiolitis, atelectasis, pneumothorax, bronchiectasis, and interstitial lung disease. We highlighted the sensitivity and specificity of lung ultrasound for the various diseases described. Furthermore, we included a comparison of this modality to other commonly used imaging techniques.

Background: Community-acquired pneumonia (CAP) is a prevalent bacterial infection in children. Lung ultrasound (LUS) is gaining popularity as a diagnostic tool for pneumonia, with the added potential for monitoring disease progression. However, research on the benefits of this modality for monitoring disease progression remains limited.

Objectives: To categorize the follow-up sonographic findings of lung inflammation in pediatric patients performed 10–14 days after being diagnosed with CAP.

Methods: We conducted a prospective observational study of children aged 0–18 years, diagnosed with CAP between 2020 and 2022. LUS findings at the time of diagnosis and 10–14 days later were recorded and documented.

Results: In total, 47 children were recruited, and 22 were included in the analysis. At the time of diagnosis, 20 patients (90%) had B-lines. Air bronchograms were found in all patients, and consolidation findings were observed in seven of the examined patients (32%). At the follow-up LUS 10–14 days later, B-lines were observed in six patients (27%). Air bronchograms were observed in eight patients, and consolidation findings were observed in six (27%). In 13 patients (59%), the follow-up LUS was completely normal. These patients were younger and had lower body weights. Pathological findings persisted in 41% of the patients.

Conclusions: For most patients, LUS demonstrated a resolution. Further large-scale studies are needed to validate the findings and determine the role of LUS in pediatric CAP.

Esophageal lung is a rare congenital malformation. We present a case of a full-term infant with an esophageal lung presenting as a white lung combined with VACTERL association (vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities) and dysmorphic features. A right pneumonectomy was successfully performed.

Inflammatory myopathies include polymyositis, necrotizing autoimmune myositis, dermatomyositis, juvenile inflammatory myopathy, and inclusion body myositis. These diseases are classified based on the different clinical and pathological characteristics unique to each of them [1]. Dermatomyositis is a rare disease with an incidence of 6–10 cases/1,000,000 a year with the highest incidence in the 7th decade of life as reported by a Norwegian cohort in a Caucasian population [2].

Diagnosis of dermatomyositis is based on typical signs and symptoms combined with laboratory results, imaging, and electromyography findings and muscle biopsy. Historically, the diagnosis of dermatomyositis was based on the classification criteria named after Bohan and Peter published in 1975. Many other classification criteria were proposed subsequently, the latter by the European League Against Rheumatism/American College of Rheumatology (EULAR/ACR), which were published in 2020 [3].

The clinical features of dermatomyositis are diverse. Skin manifestations can accompany or precede muscle weakness. Classical skin findings include periorbital heliotrope rash and a rash of the upper chest, back, and shoulders, known as the V sign and shawl sign respectively, as well as the Gottron's papules on the knuckles. Another skin appearance is subcutaneous calcifications that break periodically through the skin causing ulcerations. Dermatomyositis usually manifests as a symmetrical proximal muscle weakness but can present with preserved strength called amyopathic dermatomyositis [1].

A 69-year-old woman with a 30-year history of rheumatoid arthritis (RA) on leflunomide presented with dizziness and weakness. Vital signs, cardiopulmonary auscultation, and laboratory studies were normal. The serological status of her RA was unknown. She exhibited ulnar deviation and swan-necking of the hands but no nodular skin lesions. She was an active smoker. Chest radiography revealed an opacity in the right lung. Computed tomography (CT) showed multiple pulmonary nodules and a dominant thick-walled cavitary mass in the periphery of the right lower lobe [Figure 1A]. Due to concern for a malignancy or infection, she underwent a bronchoscopy with a biopsy of the mass, which was non-diagnostic. A subsequent transthoracic needle biopsy demonstrated a central zone of necrosis surrounded by a cuff of palisading epithelioid histiocytes with the presence of occasional giant cells [Figure 1B]. There was no malignancy, and stains for micro-organisms were negative. In this clinical context, biopsy results were consistent with a pulmonary rheumatoid nodule (PRN).

In September 2020, a 37-year-old man without significant medical history or medication use presented to the emergency department with shortness of breath. The patient denied any history of shortness of breath, travel history, recent sick contacts, or history of lung disease. On arrival, the patient was afebrile with a respiratory rate of 26 breaths per minute (b/m), oxygen saturation 82% on ambient air, blood pressure 130\80 mmHg, and heart rate 130 beats per minute (bpm). He was started on three liters per minute oxygen therapy, which improved his saturation to 90%. Physical examination was remarkable for tachypnea and diffuse bilateral inspiratory lung crackles. Electrocardiogram revealed sinus tachycardia.

Background: Intrathoracic cancer can cause hyponatremia, but it is uncertain whether mild hyponatremia in the outpatient setting should be regarded as an early sign of intrathoracic cancer.

Objectives: To evaluate the risk of undiagnosed intrathoracic cancer in patients with new persistent mild hyponatremia.

Methods: We conducted a retrospective cohort study using the electronic health record database of a large healthcare organization. The hyponatremia group included patients with sodium concentration of 130–134 mmol/L twice, after a previous normal value and without previous history of cancer or diseases related to hyponatremia. A control group with normal sodium concentration was matched by sex, age, and year of testing. We measured specific intrathoracic cancer incidence during 3 years of follow-up after sodium concentration test date. A logistic regression was used to adjust for further clinical information including smoking history, symptoms, and medications.

Results: The study comprised 1539 participants with mild hyponatremia and 7624 matched controls. New intrathoracic cancer diagnosis was more common in the hyponatremia group during a 3-year follow-up; 1.49% in the hyponatremia group and 0.39% in the control group, crude odds ratio (OR) 3.84, 95% confidence interval (95%CI) 2.22–6.63. After adjustment, hyponatremia remained a significant risk factor for the diagnosis of intrathoracic cancer; adjusted OR 3.61, 95%CI 2.08–6.28.

Conclusions: New mild persistent hyponatremia might be a significant predictive marker to a yet undiagnosed intrathoracic cancer.

Background: Late-onset pulmonary complications can occur following hematological stem cell transplantation (HSCT). In allogeneic HSCT these complications are often associated with chronic graft-versus-host disease (GVHD). Lung transplantation (LTx) often remains the only viable therapeutic option in these patients.

Objectives: To describe our experience with LTx due to GVHD after HSCT and to compare the long-term survival of this group of patients to the overall survival of our cohort of LTx recipients for other indications.

Methods: We retrospectively retrieved all data on patients who had undergone LTx for end-stage lung disease as a sequela of allogeneic HSCT, between 1997 and 2021, at Rabin Medical Center in Israel.

Results: A total of 15 of 850 patients (1.7%) from our cohort of LTx recipients fulfilled the criteria of LTx as a sequela of late pulmonary complication after allogeneic HSCT. The median age at the time of HSCT was 33 years (median 15–53, range 3–60). The median time between HSCT and first signs of chronic pulmonary GVHD was 24 months (interquartile range [IQR] 12–80). The median time from HSCT to LTx was 96 months (IQR 63–120). Multivariate analysis showed that patients transplanted due to GVHD had similar survival compared to patients who were transplanted for other indications.

Conclusions: LTx for GVHD after allogeneic HSCT constitutes an important treatment strategy. The overall survival appears to be comparable to patients after LTx for other indications.

Twenty years after being closed due to unfavorable results, a new lung transplant program was started at the Sheba Medical Center. The new team included an experienced lung transplant surgeon, an anesthesiologist, an intensive care specialist, and a pulmonologist with extensive experience in the field.

Background: The exposure to ambient particulate matter (PM) is associated with increased morbidity and mortality from respiratory, cardiovascular, and other causes. A major contribution to this adverse effect is attributed to particles at the nanoscale range (ultrafine particles [UFP] particles < 100 nm). Most of the information about human exposure to PM has been collected by environmental monitoring of inhaled particles.

Objectives: To evaluate the use of direct measuring of UFP in the sputum as a biomarker for lung inflammation and functional impairment.

Methods: The study population included 121 patients who underwent an induced sputum (IS) test as a part of a clinical evaluation for respiratory symptoms. Cell differential count was performed, and the UFP content was measured in each IS sample. The UFP content in the sputum was compared among patients with different inflammatory phenotypes based on IS granulocytes levels: eosinophilic inflammation (EI) IS eosinophils > 2.7%, neutrophilic inflammation (NI) IS neutrophils > 65%, and mixed granulocytic inflammation (MGI) including both IS eosinophils > 2.7% and IS neutrophils > 65%. The association between the IS-UFP content and pulmonary function test (PFT) parameters was also tested.

Results: Patients with MGI had a distinct profile of particles in IS, which was characterized by the highest percentage of UFP (relative to larger particles) compared to patients with EI, NI, or normal IS cell count. Furthermore, EI and NI were found to have an interaction effect regarding the IS–UFP profile, as demonstrated by the significantly different IS–UFP profile of patients with MGI compared to the profile associated with EI and NI independently. Last, the profile of UFP in the IS samples was also correlated with patient PFT. Reduced forced mid-expiratory flow (FEF) 25–75 or FEV1 were correlated with a higher IS–UFP mean size. Reduced FEF25–75 was correlated with a lower IS–UFP concentration and percentage relative to larger particles.

Conclusions: To the best of my knowledge, this study is the first to report a distinct IS–UFP profile in patients with MGI, which suggest an interaction effect of EI and NI on the IS–UFP content. This finding may further support the consideration of MGI as a distinct inflammatory phenotype, beyond the simple combination of EI and NI independently. In addition, reduced PFT parameters were associated with a specific change in the IS–UFP profile. The results of this study may shed light on the use of IS–UFP content as a biomarker for lungs inflammation and functional impairment. Further prospective studies are needed to establish a cause and effect relationship between lungs inflammation and functional impairment to the IS–UFP content.