Israel Medical Association Journal

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.

Hypereosinophilia is defined as the absolute eosinophilic count of above 1500 cells/µL in the peripheral blood on two separate tests taken during one month and/or the pathological confirmation of hypereosinophilia. There are many conditions that are associated with increased eosinophil counts including: parasitic infections, drug reactions, eosinophilic granulomatosis with polyangiitis, allergic reactions, drug reaction with eosinophilia and systemic symptoms (DRESS), primary immunodeficiencies (PID), eosinophilic gastrointestinal diseases (EGID), familial hypereosinophilia, and neoplasms [1]. Molecular classification may be an adjuvant in the classification of hypereosinophilia [2]. Our patient presented with hypereosinophilia as part of a paraneoplastic syndrome.

Background: No specific clinical or histological factors are recognized to be associated with the development of pericardial effusion in non-small cell lung cancer (NSCLC) other than a metastatic disease.

Objectives: To assess whether specific clinical and histological features are associated with development of pericardial effusion in patients with NSCLC.

Methods: A consecutive cohort of patients with NSCLC who presented with symptomatic pericardial effusion 2014–2017 was compared to a control group of patients with advanced NSCLC without pericardial effusion.

Results: The 27 patients in the effusion group were generally younger, more often female, and with a higher percentage of never-smokers, compared to the 54 patients of the control group. Epidermal growth factor receptor/anaplastic lymphoma kinase (EGFR/ALK) mutation tumors were found in 48% of patients in the effusion group vs. 25% in the control group. In the multivariate analysis, the unadjusted odds ratio (OR) for the development of pericardial effusion in patients with somatic mutations was significantly higher compared to wild type tumors (OR 2.65, 95% confidence interval 1.00–7.00). However, a suspected association between pericardial effusion and mutation status was found to be confounded by age. While a high rate of recurrence was observed when pericardiocentesis was initially performed (9/17, 53%), no recurrence was documented when pericardial window procedure was performed (total of 17 patients).

Conclusions: Patients with EGFR/ALK mutations may be at higher risk for the development of pericardial effusion; therefore, attending physicians need to be aware and have a high index of clinical suspicion

Background: Medical imaging and the resultant ionizing radiation exposure is a public concern due to the possible risk of cancer induction.

Objectives: To assess the accuracy of ultra-low-dose (ULD) chest computed tomography (CT) with denoising versus normal dose (ND) chest CT using the Lung CT Screening Reporting and Data System (Lung-RADS).

Methods: This prospective single-arm study comprised 52 patients who underwent both ND and ULD scans. Subsequently AI-based denoising methods were applied to produce a denoised ULD scan. Two chest radiologists independently and blindly assessed all scans. Each scan was assigned a Lung-RADS score and grouped as 1 + 2 and 3 + 4.

Results: The study included 30 men (58%) and 22 women (42%); mean age 69.9 ± 9 years (range 54–88). ULD scan radiation exposure was comparable on average to 3.6–4.8% of the radiation depending on patient BMI. Denoising increased signal-to-noise ratio by 27.7%. We found substantial inter-observer agreement in all scans for Lung-RADS grouping. Denoised scans performed better than ULD scans when negative likelihood ratio (LR-) was calculated (0.04–-0.08 vs. 0.08–0.12). Other than radiation changes, diameter measurement differences and part-solid nodules misclassification as a ground-glass nodule caused most Lung-RADS miscategorization.

Conclusions: When assessing asymptomatic patients for pulmonary nodules, finding a negative screen using ULD CT with denoising makes it highly unlikely for a patient to have a pulmonary nodule that requires aggressive investigation. Future studies of this technique should include larger cohorts and be considered for lung cancer screening as radiation exposure is radically reduced.