Citations

Abstract Introduction Chronic obstructive pulmonary disease involves an unregulated inflammatory process that leads to the destruction and remodeling of lung architecture, potentially resulting in air-filled lesions known as bullae. We outline a novel technique for transbronchial decompression of a bulla using robotic-assisted bronchoscopy (RAB) in a patient with intraparenchymal emphysematous bullae. Case Description A 74-year-old woman with a medical history significant for COPD, Sjögren's disease, and former smoker, presented to our outpatient clinic with progressively worsening exertional dyspnea over the past two years. The patient underwent a thymectomy for thymic hyperplasia where a right middle bulla was incidentally identified. Posterior bullectomy was not performed intraoperatively due to severe pleural adhesions and the high risk of lung injury during dissection. High-resolution chest computed tomography revealed diffuse subpleural bullous changes, with asymmetric high-attenuation mural foci in several cysts (Figure 1A), with a total volume of 124.11 cm3. Given the high surgical risk, a bronchoscopic approach was decided. Bullae needle aspiration was performed under RAB guidance. Decompression was accomplished using PleurX catheter drainage (Pleur-Evac, Telfex, USA). The connection between the robot and the drainage system utilized a 3-way stopcock (Merit Medical Systems, USA) and a 30 cm vinyl connecting tube (Cook Incorporated, USA). Suction through water seal suction was performed at 20mmHg for 5 min, during which we observed bullae reduction with live intraprocedural mobile CT images. The robot was then retracted, and a 4.0 mm Zephyr endobronchial valve was deployed in the superior segment of the right middle lobe to promote atelectasis, no immediate complications were reported. Post-procedural chest CT demonstrated a significant reduction in bullae size as shown in Figure 1B. At the one-month follow-up, chest X-ray imaging revealed increased atelectasis and persistent collapse in the previously identified area of cystic change. By the two-month follow-up, pulmonary function tests indicated nonspecific ventilatory impairment, with improvements in FEV1% (from 70.5% to 78.2%) and FVC% (from 80.5% to 90.2% of the predicted values). Subsequent follow-ups have demonstrated clinical improvement in the patient's symptoms. Conclusion We contribute to the literature by introducing a novel, non-invasive technique for managing bullae with RAB in patients who are not candidates for surgery. Further studies are warranted to standardize this technique and assess its broader applicability. Figure 1. High-resolution computed tomography showing pre- and post-procedure views of the bullae. (A) Coronal and sagittal views showing the right middle lobe bullae. (66x81mm) (B) Post-procedure view of the chest HRCT (17x29 mm)

Abstract Introduction: Prolonged mechanical ventilation can often be complicated with post-intubation tracheal stenosis (PITS). It usually manifests within few weeks following extubation. However, delayed presentations are rare and have disastrous outcomes if not identified. Early recognition of stridor and dyspnea post-extubation is crucial for timely intervention. We report a case of late presentation of PITS in a 67-year-old female patient with new-onset stridor after prolonged intubation. Case: A 67-year-old female with past medical history of coronary artery disease, type 1 diabetes, obstructive sleep apnea presented with a six-week history of progressive dyspnea on exertion and stridor. This occurred in the context of a three-week intubation following a pulseless electrical activity (PEA) arrest over five months prior. Immediately post-extubation, the patient had developed stridor without hypoxia or exertional symptoms and was subsequently discharged home without further investigation. On this presentation, she was afebrile and saturating 95% on room air with audible inspiratory stridor at bedside. Respiratory viral panel and autoimmune work up was negative. Computed tomography (CT) scan noted a significant circumferential narrowing in the proximal portion of the trachea measuring 2.5 cm in length with 0.5 cm in width with associated wall thickening. She was managed with 2.25% racemic epinephrine as needed and prednisone 10 mg daily with rescue continuous positive airway pressure (CPAP) until intervention could be safely performed after clopidogrel washout. On Day 5, she underwent rigid bronchoscopy with extensive CO2 laser vaporization (Fig. B) of scar release and paclitaxel-coated balloon dilation of the 3 mm narrowing (Fig. A) to 12 mm (Fig. C). Her stridor resolved with significant improvement in dyspnea and exercise tolerance. She was subsequently discharged on a steroid taper with outpatient interventional pulmonology follow up for repeat rigid bronchoscopy in 4 weeks to evaluate for restenosis. Discussion: Tracheostomy is often considered when extended period of intubation is anticipated as it can lead to increased risk of complications like PITS. It is important to have a high index of suspicion for tracheal stenosis in patients with a history of prolonged mechanical ventilation presenting with new-onset stridor, even when the symptoms are mild or intermittent. Early recognition and timely intervention can prevent the progression of stenosis and improve morbidity and clinical outcomes. Additionally, these patients tend to have an increased incidence of recurrence which requires close follow up for restenosis.

Abstract Rationale: Adverse social determinants of health (SDOH) are common in COPD and associated with increased mortality. However, cause-specific mortality is understudied. We evaluated associations of neighborhood-level SDOH with all-cause and cause-specific mortality among individuals with or at-risk for COPD. Methods: SPIROMICS is an ongoing, multi-center, longitudinal observational study of individuals across the US with current or former personal smoking histories (≥20 pack-years), with or without spirometrically-defined COPD. We established geocoded neighborhood-level SDOH at baseline using 2010 census tract data, including specifically, area deprivation index (ADI) (range 0-100, 100 = most disadvantaged), poverty level (percentage of households below the poverty line), poor food access (>1/3 of residents with no access to fresh food stores within 1 mile in urban areas and 10 miles in rural areas), and food desert (low income plus poor food access). We ascertained all-cause and cause-specific mortality through 12/31/2021 using the National Death Index. Using Cox proportional hazards models, we evaluated the risk of all-cause mortality for each SDOH. We utilized competing-risk regression models to evaluate the risk of cardiovascular, respiratory, COPD (a subset of respiratory), and neoplastic causes of death individually with each SDOH. Models were adjusted for demographics, smoking status, pack-years, BMI categories, coronary heart disease, FEV1% predicted and study site. Effect modification by lung function was assessed using multiplicative interactions between SDOH and FEV1% predicted. Results: Among 2977 participants, mean ADI was 40.1±27.8. Within a participant's neighborhood, on average 10.4±10.4% of households were below the poverty line, 933 (31.3%) had poor food access, and 220 (7.4%) resided in a food desert. During a median follow-up of 7.8 years (IQR 5.6-9.2), 744 (25.0%) participants died, most commonly from respiratory causes including COPD. Neither ADI nor neighborhood poverty level were associated with all-cause mortality or any specific cause of death (Table). Despite lack of associations between food access and mortality (Table), individuals residing in a food desert had elevated risks of all-cause (HR: 1.36 [95%CI: 1.03-1.79]) and cardiovascular (HR: 2.62 [95%CI: 1.5-4.35]) deaths. There was no significant effect modification by lung function. Conclusions: In a large cohort of individuals with personal smoking histories, with or without COPD, living in a food desert was associated with increased all-cause and cardiovascular mortality. However, neighborhood poverty level and food access, the two components of food desert, were not independently associated with mortality, suggesting the association of multimodal SDOH variables with mortality in this population.

Abstract Introduction: Chronic Obstructive Pulmonary Disease (COPD) exacerbations increase inflammation, immobilization, and thrombotic risk, leading to a higher incidence of pulmonary embolism (PE). This study evaluates the incidence and risk of PE in patients with acute exacerbations of COPD (AECOPD) compared to those without exacerbations. Methodology: This retrospective cohort study utilized data from 94 healthcare organizations, identifying two cohorts: patients with AECOPD and those without exacerbations. Inclusion was based on ICD-10-CM codes, and individuals with malignancies, coagulation disorders, or prior PE were excluded. Propensity score matching was performed to balance the cohorts on demographics, clinical characteristics, and medications. The primary outcome was PE incidence, analyzed using risk differences, risk ratios, odds ratios, and Kaplan-Meier survival analysis to evaluate mortality outcomes associated with PE. Results: After matching, both cohorts comprised 174,345 patients each. The mean age was approximately 73 years, with a slight female predominance (49.0% in AECOPD vs. 49.3% in non-AECOPD). The incidence of PE was significantly higher in the AECOPD cohort (15%) compared to the non-AECOPD cohort (8%) (p < 0.001). Specifically, 2,162 patients (1.3%) in the AECOPD cohort developed PE, compared to 1,467 patients (0.9%) in the non-AECOPD cohort. The risk difference was 0.004 (95% CI: 0.003, 0.005; p < 0.001). The risk ratio for PE in the AECOPD cohort was 1.477 (95% CI: 1.382, 1.577), and the odds ratio was 1.483 (95% CI: 1.387, 1.585). Survival analysis revealed a probability of 95.23% in the AECOPD cohort and 97.15% in the non-AECOPD cohort, with significant differences (χ² = 153.746, df = 1, p < 0.001). The hazard ratio for mortality associated with PE was 1.517 (95% CI: 1.419, 1.621). Conclusion: Patients with AECOPD have a significantly higher incidence of pulmonary embolism compared to those without exacerbations. PE is often overlooked in AECOPD patients due to the overlap in clinical symptoms, making timely diagnosis and treatment challenging. This can result in delayed management and poor outcomes. Therefore, it is crucial to enhance understanding of the clinical manifestations, diagnosis, and treatment of COPD complicated by PE to improve diagnostic accuracy, ensure timely intervention, and optimize patient prognosis.

Abstract Rationale: Chronic lung diseases, such as COPD and bronchiectasis (BE), may manifest differently by gender in symptom presentation, time to diagnosis, and overall disease burden. This study aimed to assess perceptions of individuals with self-reported COPD, BE, or non-tuberculous mycobacteria (NTM) regarding healthcare experiences and disease-related symptoms. Methods: This cross-sectional study analyzed data from US-based and international participants with self-reported COPD, BE, or NTM using an online survey. Participants were recruited through the COPD Foundation (COPDF) social media channels and completed a questionnaire developed with input from a steering committee that included COPDF leadership, physician-researchers, and patient stakeholders. The survey explored participants’ experiences with healthcare, disease burden, and self-reported symptoms. A subset of women answered additional questions regarding menopause-related symptom changes. Descriptive statistics were calculated and analyzed across self-identified genders and two disease groups: COPD (with or without BE or NTM) and BE (with or without NTM or COPD). Continuous variables were compared using ANOVA, while categorical variables were analyzed using chi-square or Fisher's exact test. Results: Of 632 respondents included in these analyses (mean age 70±9 years, 74% women), 68% reported COPD and 32% BE (both groups included individuals with or without additional diagnoses). Women with COPD were younger than men (p=0.048) and had a shorter duration between symptom onset and initial healthcare visit (< 6 months) (p<0.01). Compared to men, a higher proportion of women with COPD reported that their diagnosis was not explained by a healthcare provider (p=0.0381) and that they experienced anxiety, depression, or fear related to their diagnosis (p=0.0074). Among participants with BE, men and women were similar in age, though a higher proportion of men had shorter intervals (<6 months) between initial healthcare visit and confirmed diagnosis (p=0.0244) and received their diagnosis during hospitalization (p=0.0244). Both men and women across diagnoses reported similar levels of disease management burden, pulmonologist visit frequency, CAAT scores, numbers of comorbidities, and financial difficulties related to their lung condition. Over 75% of women identified as post-menopausal, with approximately one-third reporting worsening pulmonary symptoms associated with menopause. Conclusions: Despite similarities in disease management and comorbidity burden, women with BE and men with COPD reported longer times to initial healthcare visits and diagnostic delays, respectively. Additionally, over one-third of post-menopausal women experienced symptom exacerbation since menopause. These findings underscore the need to further explore gender-based differences and disparities in healthcare access and pulmonary care to enhance lung health outcomes across genders.

Abstract Introduction:IgG4-related disease (IgG4-RD) is a systemic fibroinflammatory condition marked by lymphoplasmacytic infiltrates that tend to affect various organs, leading to diverse clinical manifestations. While commonly linked to conditions like pancreatitis and sialadenitis, it can also impact the lungs, causing pulmonary masses, consolidations, or pneumonia. Key histopathological features include IgG4-positive plasma cells and storiform fibrosis, although these may not always be present. Case Presentation: We present a case of an 82-year-old male with a past medical history significant for pulmonary cryptococcal infection and a previous COVID-19 infection, who presented to our pulmonology clinic with fatigue for two months followed by an upper respiratory infection that did not respond to several rounds of antibiotics. A chest CT scan revealed bilateral consolidative airspace opacities and lymphadenopathy. Subsequent bronchoscopy with transbronchial biopsy and bronchoalveolar lavage (BAL) suggested a possible cryptococcal infection; however, his symptoms did not improve after a course of fluconazole. A follow-up PET-CT scan showed increased metabolic activity in the bilateral pulmonary consolidations, thoracic adenopathy, a possible right supraclavicular lymph node, and bilateral inguinal lymph nodes. He underwent a repeat bronchoscopy with EBUS-guided biopsy of the FDG-avid lymphadenopathy, and pathology results indicated granulomatous inflammation. He was evaluated by ophthalmology for uveitis and signs of retinal detachment on brain MRI, as well as nephrology for a progressive decline in kidney function. A renal biopsy showed numerous plasma cells staining for IgG and IgG4, along with storiform interstitial nephritis, consistent with IgG4-related interstitial nephritis. His autoimmune evaluation revealed elevated levels of ANA, double-stranded DNA, RNP antibodies, and various IgG subclasses, including IgG1, IgG3, and IgG4. Considering the biopsy results and the reduced suspicion of an infectious process, he was initiated on immunosuppression treatment with prednisone and rituximab for the IgG4-related disease which resulted in significant improvement in both the patient's symptoms and kidney function. Discussion:In conclusion, this case emphasizes the diagnostic challenges of IgG4-related pulmonary disease, largely due to the nonspecific nature of the respiratory manifestations. In our case, the diagnosis remained unclear despite the patient undergoing both transbronchial and EBUS-guided lymph node biopsies. This highlights the importance of maintaining a high clinical suspicion for this underdiagnosed condition as early treatment can lead to notable recovery.

Abstract Background Pneumocystis jirovecii pneumonia (PJP) is commonly seen in immunocompromised patients. Telomere biology disorder (TBD), which is a genetic disorder marked by mutations in telomere-maintenance genes, leading to shortened telomere, accelerated aging, and multi-systems effects including the pulmonary and immune systems. Idiopathic pulmonary fibrosis (IPF) is the most common pulmonary manifestation in TBD. Opportunistic infections, such as PJP, occurring de novo are rare in TBD, presenting unique diagnostic and therapeutic challenges. Case Presentation We present a female in her seventies with chronic dry cough and exertional dyspnea referred for evaluation of interstitial lung disease (ILD). Her family history revealed early-onset pulmonary fibrosis in her mother and sister. A year before the presentation, she developed acute hypoxic respiratory failure with bilateral pulmonary infiltrates. Bronchoalveolar lavage confirmed PJP despite no established immunosuppression. She received Bactrim and prednisone without clinical improvement. High-resolution chest CT revealed progressive infiltrates and fibrotic lung disease. Surgical lung biopsy showed organizing pneumonia, diffuse alveolar damage, and fibrosis, consistent with probable usual interstitial pneumonia (UIP). Ultimately, she developed rapidly progressive ILD. Further evaluation ruled out autoimmune and connective tissue disease. Telomere studies confirmed TBD, with her lymphocyte and granulocyte telomere lengths between the 1st and 10th percentiles. (figure1) Genetic testing is underway for familial pulmonary fibrosis. Discussion This case illustrates a rare presentation of PJP de novo in a patient with TBD, highlighting opportunistic infections risk in those patients without immunosuppression and before transplantation. TBD results in quantitative and qualitative T-cell immunodeficiency, reducing CD4+ T-cell count, predisposing to opportunistic infections, including PJP. TBD patients often experience a rapidly progressive course of ILD due to inherited telomere dysfunction causing limited regenerative capacity of Alveolar epithelial type 2 cells (AEC2s) exacerbated by environmental or age-related factors such as oxidative stress or smoking. Management requires a multidisciplinary approach with early genetic testing, antifibrotic therapies, and prophylactic treatments to prevent infections. This case underscores the importance of considering TBD in patients with opportunistic infections like PJP in the absence of traditional immunosuppressive risk factor and in patients with premature or progressive pulmonary fibrosis. Conclusion Telomere biology disorder can present with rapidly progressive ILD with atypical infections like PJP while on immunosuppression. To the best of our knowledge de novo PJP pneumonia in patient with TBD is unreported in the literature. High clinical suspicion, quantitative CD4 evaluation and consideration of PJP prophylaxis prevent an otherwise fatal outcome. Figure1:

Abstract Introduction: Acute Eosinophilic pneumonia (AEP) is an eosinophilic pulmonary condition defined by symptoms of less than or equal to 1 month's duration, pulmonary infiltrates on imaging, pulmonary eosinophilia of 25% or greater on bronchoalveolar lavage (BAL) cell count or eosinophilic pneumonia on lung biopsy, and absence of other eosinophilic pulmonary diseases. It can be associated with a multitude of exposures, including medications, inhalants as well as systemic conditions. We report a case of AEP associated with intramuscular (IM) progesterone administration. Case: A 36-year-old female presented to the emergency department with dyspnea on exertion, cough productive of yellow sputum, and subjective fever of two days’ duration. She had undergone in vitro fertilization using IM Progesterone as luteal phase support and experienced a miscarriage one week prior. She had a heart rate of 132 and required oxygen at 2 Liters per minute via nasal cannula to maintain her saturation at 92%. Her complete blood count showed an absolute eosinophil count of 1800 cells/uL. She underwent a computed tomography angiography scan of the chest, which was negative for a pulmonary embolism but showed diffuse bilateral peripheral ground-glass opacities as well as consolidations in both lung bases. She was empirically started on prednisone 40 mg per day. She later underwent a flexible bronchoscopy with BAL of the right middle lobe as well as transbronchial cryobiopsies of the right lung. The BAL cell differential showed 63% eosinophils confirming the diagnosis of AEP. Pathology revealed patchy organizing pneumonia with scattered eosinophils. Autoimmune workup was negative, including antineutrophil antibodies, Anti-myeloperoxidase, and anti-proteinase-3 antibodies. Infectious workup, including blood, sputum, and BAL cultures, was also negative. The patient dramatically improved with steroid administration. Her symptoms resolved, and she was discharged on room air with a 4-week prednisone taper. A follow-up chest x-ray revealed resolution of the infiltrates. Discussion: AEP is a rare condition. One epidemiological study estimated the incidence of AEP at 9.1/100,000 person-years in a population of United States military personnel. Given the lack of other inciting medications and negative autoimmune and infectious workup, IM progesterone administration was deemed the likely etiology of her presentation. There are four case reports of IM progesterone as a cause of AEP. This case represents a classic presentation of AEP with the secondary to progesterone administration and with symptoms resolving promptly with steroid administration.

Abstract Introduction: Birt-Hogg-Dube (BHD) is a rare autosomal dominant genetic disorder caused by mutations in the FLCN tumor suppressor gene. Clinically, BHD is characterized by development of cutaneous fibrofolliculomas/trichodiscomas, renal tumors, and pulmonary cysts, the latter which can result in recurrent, spontaneous pneumothoraces. We present a case of BHD in which diagnosis was delayed given absence of dermatologic and renal manifestations. Case Report: A 66-year-old female never smoker with a past medical history of left-sided breast cancer treated with lumpectomy and chemoradiation and osteoporosis presented for evaluation of recurrent pneumothoraces. Her first pneumothoraces occurred in her 20s-30s and required doxycycline pleurodesis (right side) and video-assisted thoracoscopic pleurodesis (left side). The most recent pneumothorax was in her 50s and resolved with chest tube placement. She reported repeated episodes of pneumonia which prompted pulmonary re-evaluation. A non-contrast CT chest was obtained which demonstrated middle and lower lobe predominant irregular thin-walled cystic changes with paramediastinal involvement. Pulmonary function testing revealed mild hyperinflation but otherwise no evidence of obstruction, restriction, or diffusion limitations (FEV1 113% predicted, FEV1/FVC of 0.72 predicted, FVC 109% predicted, TLC 108% predicted, DLCO 90% predicted). Immunoglobulins and alpha-1 antitrypsin were obtained and normal. A lung biopsy was discussed for definitive diagnosis but never performed. Upon presentation to our clinic, she reported no symptoms such as cough, shortness of breath, pleuritic chest pain, fevers, arthralgias, myalgias, rashes, dry mouth, or dry eyes. A broad differential was considered and a connective tissue disease cascade, VEGF-D testing, and SPEP/UPEP were sent and negative/normal. Given the distribution of cysts on her CT, BHD was considered, and she was referred to clinical genetics for germline testing which identified a heterozygous FLCN variant (c.837dup, p.Glu280Argfs[asterisk]12) consistent with BHD. Discussion: BHD is a rare and underdiagnosed cause of cystic lung disease as it has a broad range of clinical manifestations. Recognizing the disease without either renal or dermatologic manifestations as in our patient can be challenging and requires a high degree of suspicion. Clues to the diagnosis include a family history of spontaneous pneumothorax, which can be highly predictive of BHD as it is the most common cause of hereditary pneumothorax. Definitive diagnosis of BHD depends on a combination of clinical features and germline testing for mutations in the FLCN gene.

Abstract Introduction EGPA is diagnosed clinically in patients with asthma, rhinosinusitis, and eosinophilia with end-organ involvement including neuropathy, lung infiltrates, cardiomyopathy, or kidney, gastrointestinal, or skin involvement. The five-factor score (FFS) differentiates non-severe (FFS = 0) and severe (FFS > 0) EGPA. Forme fruste, or partially treated, EGPA occurs when presumed severe eosinophilic asthma is treated with corticosteroids that can mask end organ damage typical of EGPA. We present a case of forme fruste non-severe EGPA that failed established treatments for non-severe and severe EGPA. Case Presentation This is a 38-year-old female presenting to the pulmonology clinic with three years of cough, dyspnea, wheezing, rhinorrhea, and chest heaviness. She was initially given prednisone for adult-onset asthma with improvement but was unable to taper due to symptom recrudescence on doses lower than 20 milligrams. Allergic bronchopulmonary aspergillosis testing was negative, fractional exhaled nitric oxide was elevated, pulmonary function testing showed moderate airway obstruction, and absolute eosinophil count was 11x10^3/microliter despite prednisone use. Chest computed tomography (CT) showed mild bronchial wall thickening. She was given benralizumab followed by mepolizumab, inhaled corticosteroid with a long-acting beta agonist, cetirizine, nasal budesonide, and two cycles of rituximab for possible EGPA at an outside hospital. At the current evaluation, Chest CT showed multiple nodules, patchy ground glass opacities, and bronchial wall thickening. CT sinuses showed paranasal sinus mucosal thickening with sinus outlet obstruction and nasal endoscopy showed polyps. Anti-neutrophil cytoplasmic antibody was negative, urinalysis showed mild hematuria, and bronchoalveolar lavage was negative for infection. Bone marrow did not suggest neoplasm and hematology workup did not identify other causes of hypereosinophilia. EGPA was considered highest on the differential. She was offered sinus surgery and lung biopsy for enrollment in refractory EGPA trials, but no further medical therapy was identified. Discussion This case shows the importance of recognizing potential forme fruste EGPA rather than asthma refractory to systemic glucocorticoids. Early suspicion is crucial to initiation of the proper regimen. Non-severe EGPA warrants treatment with corticosteroids and mepolizumab. Azathioprine and cyclophosphamide have demonstrated a comparable benefit in relapsing non-severe EGPA after steroid treatment, but in a single low power study. In our patient, who was refractory to glucocorticoids with mepolizumab and rituximab, there is no strong data suggesting further treatment not involving high dose steroids. In her case, chronic steroid use led to morbid obesity and obstructive sleep apnea, highlighting the importance of further research in non-severe EGPA treatment.