Israel Medical Association Journal

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal lung disease leading to end-stage lung disease (ESLD). Single lung transplantation (SLT) is the primary treatment option for IPF; however, the native lung continues to influence post-transplant outcomes.

Objective: To determine whether the native lung continues to deteriorate under post-transplantation immunosuppression treatment by assessing chest computed tomography (CT) and perfusion scans.

Methods: We conducted a single-center retrospective analysis of patients who underwent SLT for IPF between 2016 and 2023. Serial chest CT scans assessed native lung changes. CT signs of fibrosis were scored for severity according to published criteria for defining pulmonary fibrosis disease progression. Lung volumes and perfusion were calculated.

Results: Among 57 patients (mean age 57 years; 33% female), 42% died during follow-up (median survival 95 months). The most common immunosuppressive regimen (54% of patients) included prednisone, calcineurin inhibitor, and mycophenolate mofetil. CT analysis demonstrated that in 41/57 (72%) patients, fibrosis signs continued to deteriorate. There was also a significant correlation decline in native lung volume and perfusion scans over time (P = 0.0003, P < 0.0001, respectively) (r = 0.82, P = 0.03).

Conclusions: Fibrotic progression in the native lung persists after SLT as demonstrated by both chest CT and nuclear perfusion scan, thus highlighting the importance of ongoing monitoring for accuracy and complications assessment, integrating it into routine surveillance, and ensuring it is consistently considered in post-transplant assessments.

Pulmonary medicine, a major subspecialty of internal medicine, has advanced dramatically over the past decade and continues to grow at an impressive pace. The subspeciality is a uniquely multifaceted field, requiring thoughtful integration of the patient’s history, physical findings, laboratory data, and imaging to reach an accurate diagnosis and suggest proper treatment. This clinical depth is complemented by a rapidly expanding therapeutic arsenal for complex lung diseases. At the same time, technological progress has transformed our practice. Innovations in imaging and in both diagnostic and therapeutic bronchoscopy–central components of interventional pulmonology–have evolved so rapidly that tools used only a decade or two ago now seem outdated [1]. All these advancements offer meaningful opportunities to enhance the health outcomes of our patients. What a fascinating specialty and what an exciting time to be a pulmonologist.

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: Patients with chronic obstructive pulmonary disease (COPD) have an increased risk of cardiovascular events, especially following acute exacerbation (AECOPD). However, there is insufficient data to identify high-risk subjects.

Objectives: To evaluate the association between neutrophil-to-lymphocyte ratio (NLR), a marker of inflammation, and the risk of cardiovascular events following exacerbation.

Methods: This retrospective cohort included patients with COPD who were hospitalized with AECOPD between January 2016 and December 2022. We took the reference NLR before index admission and evaluated the incidence of major adverse cardiovascular events (MACE) or cardiovascular death over the following year. Multivariate analysis and competing risk regression were used to assess hazard ratio (HR) and NLR threshold for increased cardiovascular risk.

Results: In total, 15,224 patients with AECOPD completed one 1-year follow-up session. The majority were male (54%) with a mean age of 69 ± 3 years. The risk for MACE of patients in the highest NLR quartile was higher over the first year following AECOPD; however, the magnitude of effect decreased over time. After adjustment to other confounders that may increase NLR, a value > 3.5 was found with the strongest predictive power

Conclusion: Community NLR can be used to identify patients at increased risk of cardiovascular events following AECOPD, together with other risk factors. Every effort should be made to reduce exacerbation risk, and target intervention to those patients at highest risk.

Background: Interpretation of blood gases is essential for the correct practice of medicine. Normal ranges for arterial blood gases (ABG) have not been extensively studied in the older population. Also, venous blood gases and venous-arterial pCO₂ gradient have not been studied in this population, even though they signify the majority of hospitalized patients.

Objectives: To determine the normal range for ABG and the bias limits of agreement for arterial-venous difference in the elderly population.

Methods: We recruited 130 elderly patients (> 70 years) and obtained blood gas measurements from venous and arterial blood. Patients were divided into four categories: healthy patients, patients with stable chronic pulmonary disease, hospitalized patients with acute respiratory illness, and hospitalized patients without respiratory disease. Samples were analyzed in a point of care analyzer.

Results: Mean PaCO₂ was 36.9 ± 4.2 mmHg for the healthy control group, 37.0 ± 4.8 mmHg in the stable chronic respiratory group, 37.0 ± 5.0 mmHg in the non-respiratory hospitalization group, and 42.3 ± 11.4 mmHg for the respiratory hospitalization group, Kruskall-Wallis, P <0.0025. Mean bias between venous and arterial CO₂ was +10.0 mmHg with 95% limits of agreement between 2.7 mmHg and -22.8 mmHg.

Conclusions: In elderly patients, the range of PaCO₂ measurements was similar to the accepted normal range in clinical practice. Venous-arterial PCO₂ gradient had high bias and wide limits of agreement, similar to previously published studies.

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.

Chronic obstructive pulmonary disease (COPD) is a disease state characterized by persistent respiratory symptoms and airflow obstruction determined by spirometry, including emphysema, chronic bronchitis, and small airway disease. Traditional treatment settings for COPD exacerbations typically involve in-hospital care. However, hospital-at-home (HaH) programs have emerged as an innovative model to provide hospital-level care at a patient's home. I synthesized available randomized controlled trials (RCTs) and compared the outcomes of COPD management in HaH and in-hospital settings. I searched for English language medical literature studies of COPD patients in HaH programs compared to in-hospital. Searches were performed in PubMed, EMBASE, Scopus, and CENTRAL. Outcomes were compared, meta-analyses were performed, and pooled odds ratios (ORs) and 95% confidence intervals (95%CIs) were calculated. Heterogeneity was evaluated and I² statistic was used to measure the proportion of inconsistency in individual studies. Potential publication bias was also calculated. Seven controlled studies representing 19 sub-studies (data sets) were selected according to the inclusion criteria. The OR of the HaH and in-hospital comparison was 0.542, 95%CI 0.379–0.774, P = 0.001. The different clinical outcomes of HaH were better or similar to those at regular hospitals, but with higher patient preference (OR 0.316, 95%CI 0.198–0.506). Heterogeneity and inconsistency were small, with no significant publication bias. HaH may be recommended for COPD patients' hospitalization when needed according to the specific indications and patients matching HaH criteria.

We presented the emergent development of pulmonary hypertension and right ventricular impairment in a 64-year-old woman with metastatic breast cancer undergoing carboplatin–gemcitabine combination therapy. The patient's acute decompensation, characterized by dyspnea and desaturation, occurred 2 days after chemotherapy initiation. Clinical assessments revealed right ventricular dilation and systolic dysfunction, a rare manifestation not previously associated with the administered drugs, but which may be associated with cardiopulmonary toxicity of gemcitabine therapy. Prompt discontinuation of chemotherapy and initiation of diuretic therapy resulted in clinical improvement and resolution of the right ventricular dysfunction within several weeks. While a definitive causal link to gemcitabine remains inconclusive, this report highlights a potential and under-reported side effect, emphasizing the need for increased awareness and further investigation into the cardiopulmonary effects of gemcitabine.

A full-term 1-month-old female was brought to our pediatric emergency department (ED) due to 3 days of increasing respiratory distress. She was born at term to healthy, consanguineous (2nd degree) Bedouin parents after a pregnancy that lacked adequate monitoring. At birth, a physical examination revealed an imperforate anus and a recto-vestibular fistula, left hydronephrosis, large patent ductus arteriosus (PDA), and an atrial septal defect (ASD). The diagnosis of VACTER association was made. Importantly, she had no respiratory difficulties, nor hemivertebra or tethered cord.

On admission to the ED, she presented with severe respiratory distress, tachypnea, dyspnea, and hypoxemia without evidence of upper airway obstruction or stridor. Due to impending respiratory failure, she was transferred to the pediatric intensive care unit and started on non-invasive respiratory support through a high-flow nasal cannula (HFNC), which partially relieved her work of breathing. The nasal swab for respiratory viruses was positive for enterovirus, and her urine culture grew Escherichia coli. She was transferred to the pediatric ward after clinical improvement on day 3. Echocardiography performed for evaluation of pulmonary hypertension estimated normal pressures but revealed a vascular ring anomaly. A computed tomography (CT) angiography performed confirmed the presence of an aberrant left pulmonary artery also referred to as a left pulmonary artery sling (LPAS) [Figure 1A].

Peripartum cardiomyopathy (PPCM) is an idiopathic cardiomyopathy presenting with heart failure (HF) secondary to left ventricular systolic dysfunction (defined as left ventricular ejection fraction [LVEF]) < 45% toward the end of pregnancy or in the months following delivery, where no other cause of HF is found. Complete understanding of the etiology is lacking, with higher incidence seen in advanced maternal age, multiple gestations, preeclampsia, and anemia [1]. Potential suggested causes include pathological immune response, hormonal abnormalities, stress cytokines, and nutritional deficiencies. Genetic predisposition was demonstrated in some PPCM, most commonly pathogenic loss-of-function truncating variants in Titin gene (TTN) [1]. Other causative genes reported are DMD, LAMP2, DSP, MYH6, SYNM, TPM1, and VCL [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).

Background: Pulmonary aspiration is a potentially lethal perioperative complication that can be precipitated by gastric insufflation. Face mask ventilation (FMV), a ubiquitous anesthetic procedure, can cause gastric insufflation. FMV with an inspiratory pressure of 15 cm H₂O provides the best balance between adequate pulmonary ventilation and a low probability of gastric insufflation. There is no data about the effects of FMV > 120 seconds.

Objectives: To investigate the effect of prolonged FMV on gastric insufflation.

Methods: We conducted a prospective observational study at a tertiary medical center with female patients who underwent oocyte retrieval surgery under general anesthesia FMV. Pre- and postoperative gastric ultrasound examinations measured the gastric antral cross-sectional area to detect gastric insufflation. Pressure-controlled FMV with an inspiratory pressure of 15 cm H₂O was continued from the anesthesia induction until the end of the surgery.

Results: The study comprised 49 patients. Baseline preoperative gastric ultrasound demonstrated optimal and good image quality. All supine measurements were feasible. The median duration of FMV was 13 minutes (interquartile range 9–18). In the postoperative period, gastric insufflation was detected in only 2 of 49 patients (4.1%). There was no association between the duration of FMV and delta gastric antral cross-sectional area (β -0.01; 95% confidence interval -0.04 to 0.01, P = 0.31).

Conclusions: Pressure-controlled FMV with an inspiratory pressure of 15 cm H₂O carries a low incidence of gastric insufflations, not only as a bridge to a definitive airway but as an alternative ventilation method for relatively short procedures in selective populations.

Chronic obstructive pulmonary disease (COPD) is a common lung disease characterized by restricted airflow, changes of lung tissues, and breathing difficulties [1]. Most patients are treated at home to maintain a stable lifestyle and quality of life [2].

An important feature of COPD is exacerbation, which is an acute worsening of symptoms that can result in decreased pulmonary functions, increased risk of death, and poorer quality of life. The frequency and severity of each exacerbation results in further worsening of pulmonary function [3]. Depression in COPD patients may cause objective impairment in function and decreased adherence to therapeutic interventions [4].

Acute stress disorder is characterized by acute reaction in the first month following exposure to a traumatic event such as threatened death, serious injury, or sexual assault. Symptoms include intrusion, dissociation, negative mood avoidance, and arousal [5]. Stress on a more continuous basis can significantly debilitate a person's emotional and physical wellbeing, lead to depression and weakened immune system, and influence patients with already stressful and progressive conditions such as COPD.

We present a patient previously diagnosed with COPD who experienced an acute terror attack, which was a major and stressful event that caused severe exacerbation of the disease.

Metastatic pulmonary calcinosis (MPC) is characterized by deposits of calcium in normal pulmonary parenchyma. Diffuse pulmonary calcinosis commonly occurs in hypercalcemia and/or hyperphosphatemia and is more commonly related to renal failure than primary hyperparathyroidism, skeletal metastases, or multiple myeloma [1]. Calcium depositions favor alkaline tissue and are thus more common in the upper lobes of the lung, which have a higher ventilation to perfusion ratio and a low capillary pCO₂, resulting in an alkaline pH [2]. Therefore, the most common radiographic manifestation consists of poorly defined nodular opacities bilaterally in the upper lung zones [3].