Pulmonary Comorbidities Research Articles

The Impact of Poor Air Quality on Hospitalisation of Multi-morbid Patients: A Systematic Review

Abstract Background Exposure to poor air quality worsen existing health conditions, particularly amongst vulnerable patients, leading to increased healthcare utilization. We conducted a systematic review to explore the impact of exposure to poor quality on healthcare requirements in multi-morbid patients. Methods We searched six major databases (Medline via Ovid, Embase via Ovid, Web of Science, CINAHL, Global Health, and Scopus) using search terms grouped into sets relating to ‘air pollution,’ ‘multimorbidity,’ “association” and ‘hospitalisation.’ We were interested in the impact of common air pollutants (PM2.5, PM10, SO2, NO2, O3, and CO) and articles were screened independently by two researchers. The review was registered with The International Prospective Register of Systematic Reviews (CRD42022369757) and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results A total of nineteen studies were included. All six air pollutants increased hospitalisation amongst multi-morbid patients, especially those with diabetes and cardiovascular comorbidity. Females and the elderly (>65 years old) were the most vulnerable to the effects of air pollution, with an increase in hospitalisations of 9.23% and 6.35% when exposed to PM2.5 and PM10, respectively. Patients >65 years had a higher likelihood of hospitalisation for ischemic and haemorrhagic stroke when exposed to PM2.5 or PM10 at warm season. Patients (≥70 years) who had cardiovascular and pulmonary comorbidity were 3.9% more likely to be hospitalised for a cardiopulmonary event with a rise in NO2 levels. We found an intersectional effect (referred to as “the CADC effect” - Climatic changes, Air pollutant, Demographics, Chronic conditions) that influenced the likelihood of hospitalisation. Conclusions Future research is required to further understand this CADC effect in other high-risk population. Key messages • Females, elderly, those with cardiovascular, and pulmonary comorbidity are at the highest risk of hospitalisation with poor air quality. • The CADC effect explains the intersectional effect between hospitalisation in multimorbid patients, patients demographics and chronic conditions, and air pollution and temperature effects.

Pulmonary outcomes of incretin-based therapies in COPD patients receiving single-inhaler triple therapy

IntroductionPatients with chronic obstructive pulmonary disease (COPD) on triple therapy often face exacerbations and comorbidities. Emerging evidence suggests that glucagon-like peptide-1 (GLP-1) analogs may reduce the risk of exacerbation in patients with COPD and type 2 diabetes mellitus (T2DM). This study investigates the impact of GLP-1 analogs on pulmonary outcomes in patients with COPD on single-inhaler triple therapy (SITT) and T2DM.MethodsWe conducted a retrospective cohort study using the TriNetX database and analysed adult patients with COPD and T2DM who received SITT between April 2005 and July 2023. Patients were categorized into GLP-1 analog and dipeptidyl peptidase-4 inhibitors (DPP4i) cohorts. The primary efficacy outcome was COPD exacerbation and the secondary efficacy outcomes were pneumonia, acute respiratory distress syndrome, intubation, oxygen dependence, and all-cause mortality. The secondary outcomes were serious gastrointestinal adverse events.ResultsWe included 6898 patients, with 4184 receiving GLP-1 analogs and 2714 receiving DPP4i. After matching, 1751 GLP-1 analog users were matched with 1751 DPP4i users. GLP-1 analog users had an 18% lower risk of COPD exacerbation (hazard ratio [HR], 0.82 [95% CI: 0.71–0.94]), a 28% reduced risk of pneumonia (HR, 0.72 [95% CI: 0.61–0.85]), a 34% reduced risk of oxygen dependence (HR, 0.66 [95% CI: 0.47–0.91]), and a 40% decreased risk of all-cause mortality (HR, 0.60 [95% CI: 0.47–0.77]). No significant serious gastrointestinal adverse events were observed.ConclusionGLP-1 analogs may be associated with reduced COPD exacerbations, pulmonary comorbidities, and mortality in patients with COPD receiving SITT and T2DM, with no significant serious gastrointestinal safety concerns.

Precision patient selection for improved detection of circulating genetically abnormal cells in pulmonary nodules.

Circulating genetically abnormal cells (CACs) have emerged as a promising biomarker for the early diagnosis of lung cancer, particularly in patients with pulmonary nodules. However, their performance may be suboptimal in certain patient populations. This study aimed to refine patient selection to improve the detection of CACs in pulmonary nodules. A retrospective analysis was conducted on 241 patients with pulmonary nodules who had undergone pathological diagnosis through surgical tissue specimens. Utilizing consensus clustering analysis, the patients were categorized into three distinct clusters. Cluster 1 was characterized by older age, larger nodule size, and a higher prevalence of hypertension and diabetes. Notably, the diagnostic efficacy of CACs in Cluster 1 surpassed that of the overall patient population (AUC: 0.855 vs. 0.689, P = 0.044). Moreover, for Cluster 1, an integrated diagnostic model was developed, incorporating CACs, sex, maximum nodule type, and maximum nodule size, resulting in a further improved AUC of 0.925 (95% CI 0.846-1.000). In conclusion, our study demonstrates that CACs detection shows better diagnostic performance in aiding the differentiation between benign and malignant nodules in older patients with larger pulmonary nodules and comorbidities such as diabetes and hypertension. Further research and validation are needed to explore how to better integrate CACs detection into clinical practice.

Optimized anti-tuberculosis duration for drug-susceptible pulmonary tuberculosis-diabetes mellitus comorbidities: study protocol for a multicenter randomized controlled trial

BackgroundThe coexistence of tuberculosis (TB) and type 2 diabetes mellitus (DM) presents unique challenges in treatment optimization and management, given the mutual exacerbation of disease processes.ObjectiveThis multicenter, open-label, randomized controlled trial aims to evaluate the efficacy and safety of two different treatment durations (6-month versus 9-month regimens) regimen for patients with drug-susceptible pulmonary tuberculosis (DS-PTB) and concurrent type 2 diabetes (DM).MethodsPatients with DS-PTB and type-2 DM from 22 hospitals in China are enrolled. They are randomized in a 1:1 ratio into either the 6-month regimen arm(2HRZE/4HR) or the 9-month regimen arm(2HRZE/7HR). At the end of the intensive phase (the 8th week), patients in both arms who with sputum positive smear will extent one more month of intensive treatment. The primary outcome is the proportion of unfavorable outcomes at 24 months after randomization. Secondary outcomes include treatment success rate at the end of treatment, proportion of recurrence at 24 months after randomization, time to recurrence after treatment completion, proportion of intensive phrase extension, occurrence of adverse events grade 3 or above during treatment.DiscussionThe study focuses on assessing the optimal treatment duration to maximize treatment success while minimizing recurrence and adverse events. The trial is expected to provide vital insights into the appropriate treatment duration for patients with TB-DM, aiming to reduce recurrence rates and improve overall treatment outcomes in this vulnerable population.Trail registrationChictr.org.cn, ChiCTR2100044663. Registered on March 25, 2021.

WP2.14 - Lung Mycetoma - Chronicles from the Pandemic

Abstract Introduction COVID-19 is a global pandemic which obeys no geographical borders. Post Covid pneumonia sequalae is still an unpredictable course especially with patients with a pre-existing lung compromise. In such scenario, a cohort of patients must also be looked for a fungal infection. Case Study A 31-year-old male presented with history of fever, hemoptysis, and weight loss for 1 month. He suffered from Covid-19 pneumonia 3 months back. He was also diagnosed with Pulmonary tuberculosis 4 years back. Examination revealed right sided tracheal deviation with dull percussion note on the upper and middle zones of the right side of chest. Pulmonary function tests showed a restrictive pattern with a FEV1/FVC ratio of 0.9 (FEV1=2.02, FVC=2.22). Transthoracic echocardiography revealed dextrocardia, moderate TR, and a pulmonary arterial systolic pressure of 25 mm Hg. Contrast enhanced CT scan of thoracic cavity showed reduced right hemithorax, well-defined thick-walled cavities in the upper and lower lobe of the right lung and a ground glass appearance in the bilateral lower lobes. A diagnosis of Lung mycetoma was made along with post covid-19 pneumonia changes. Right posterolateral thoracotomy and right pneumonectomy was performed. Per-operatively, a collapsed lower lobe and stony hard upper and middle lobes of right lung with associated fungal balls were found. Patient was clinically well after a 30-day follow-up period. Conclusion Covid-19 patients with pre-existing pulmonary co-morbidities should be followed with caution and pulmonary symptoms in the post pneumonia patient should raise the suspicion of fungal infections as well.

Medical Costs of Nontuberculous Mycobacterial Pulmonary Disease, South Korea, 2015-2019.

Nontuberculous mycobacterial pulmonary disease (NTM-PD) prevalence is a rising public health concern. We assessed the long-term healthcare systems perspective of costs incurred by 147 NTM-PD patients at a tertiary hospital in South Korea. Median cumulative total medical cost in managing NTM-PD patients was US $5,044 (interquartile range US $3,586-$9,680) over 49.7 months (interquartile range 33.0-68.2 months) of follow-up. The major cost drivers were diagnostic testing and medication, accounting for 59.6% of total costs. Higher costs were associated with hospitalization for Mycobacterium abscessus infection and pulmonary comorbidities. Of the total medical care costs, 50.2% were patient co-payments resulting from limited national health insurance coverage. As South Korea faces significant problems of poverty during old age and increasing NTM-PD prevalence, the financial and socio-economic burden of NTM-PD may become a major public health concern that should be considered with regard to adequate strategies for NTM-PD patients.

P183 PERIPARTUM CARDIOMYOPATHY: MONOCENTRIC DESCRIPTION AT THE NORTHERN REGIONAL MATERNITY HOSPITAL OF THE DOMINICAN REPUBLIC

Background: Peripartum cardiomyopathy (PPCM) is a pathology in which the woman's heart dilates and displays signs and symptoms of heart failure. It is a rare pathology, with a high mortality rate, and predominance in black patients. Its diagnosis and management are not standardized, nor adapted to low income countries. This leads to barriers in identifying and treating the disease in higher-risk countries such as Haiti, making it a relevant issue in the Dominican Republic due to high immigration of haitians to the country. Therefore we aimed to evaluate the association of risk factors and the pharmacological regimen of patients in a public healthcare center in the Dominican Republic. Methods: An observational, retrospective, cross-sectional study was carried out with convenience sampling. This included patients who had been admitted to the Presidente Estrella Ureña Regional Hospital with suspected PPCM during the last 3 years. Variables studied include: sociodemographic factors, toxic habits, pathological and gynecological-obstetric history, cardiovascular, pulmonary and general signs and symptoms. Results: A sample of 19 patients with a median age of 27 years was obtained, 73.4% of them were black. All of the patients who had illness onset in the peripartum period (first 28 days after labor) presented adverse events, infectious comorbidities and “other comorbidities” while 75% of them presented cardiac and pulmonary comorbidities. Regarding treatment, only 77.8% of patients with antepartum onset received treatment in this period. Additionally, 66.7% of patients with antepartum onset developed adverse events that required oxygen-supplementation, versus only 33% of those without adverse events. Conclusions: It is relevant to design tools for calculating the risk of developing PPCM and standardize its disparate diagnosis and treatment, particularly aimed at countries with limited resources. This aims to improve the prognosis in patients with risk factors such as: black race, age over 30 years and living in low/middle-resource countries.

466. ROBOT-ASSISTED CERVICAL ESOPHAGECTOMY (RACE) FOR ESOPHAGEAL CANCER: THE FIRST TWO CASES OF AN ITALIAN HIGH-VOLUME CENTER

Abstract Background Closed thorax esophagectomy is an alternative to conventional two or three-field esophagectomy in patients with esophageal cancer and pulmonary comorbidities, previous thoracic surgery or cervical tumor spread without thoracic involvement. We describe our first two cases of robotic trans-hiatal and trans-cervical esophagectomy. Methods We performed a robotic assisted abdominal D2 lymphadenectomy and trans-hiatal esophageal dissection until the tracheal carina with en bloc mediastinal lymphadenectomy. Then we did left cervicotomy and, using a gelPort, we continued robotic esophageal dissection in superior mediastinum until the carina, preserving left recurrent nerve. Subsequently, in abdomen, we completed esophageal dissection and gastric tubulization. After section of the esophagus we pulled up the gastric conduit and in one case we performed a esophago-gastric 23 mm termino-lateral mechanical circular anastomosis and in the other hypopharyngeal-gastric handsewn double layer anastomosis. Results One patient had distal esophageal adenocarcinoma and we chose RACE because of previous pleuritis. Pathology reported ypT2N1 (35 lymph nodes retrieved) with R0 resection. Post operative complications were cervical anastomotic leak, chylous ascites and atrial fibrillation treated conservatively; total length of stay (LOS) was 25 days. The second patient had cervical squamous cell carcinoma spreading to the neck without thoracic involvement. In addition to RACE, we performed tracheostomy after cervical lymphadenectomy. Pathology reported ypT0N0 (17 lymph nodes) with R0 resection. A post-operative Bernard Horner syndrome was noted; total LOS was 16 days. Conclusion Our first experience in performing RACE with the Da Vinci Xi robotic system shows that this can be a feasible procedure with adequate surgical and oncological outcomes. Further comparison studies are needed.

Safety and efficacy of riociguat in patients with pulmonary arterial hypertension and cardiometabolic comorbidities: Data from interventional clinical trials

BACKGROUNDThere is limited evidence to support treatment recommendations in patients with pulmonary arterial hypertension (PAH) and comorbidities. To investigate the impact of riociguat treatment in this patient population we analyzed pooled data from randomized controlled trials of riociguat. METHODSThis post hoc analysis included data from the PATENT-1, PATENT-2, PATENT PLUS, and REPLACE studies. Safety, efficacy (6-minute walk distance [6MWD], World Health Organization functional class [WHO-FC], and N-terminal pro-brain natriuretic peptide [NT-proBNP]), and COMPERA 2.0 risk status were assessed in patients with 0, 1–2, or 3–4 cardiometabolic comorbidities (obesity, systemic hypertension, diabetes mellitus, coronary artery disease) in the main phase of the studies. Safety was also assessed in the long-term extensions. RESULTSThe analysis included 686 patients (riociguat, n = 440; placebo, n = 132; phosphodiesterase type 5 inhibitors [PDE5i], n = 114), of whom 55%, 39%, and 6% had 0, 1–2, and 3–4 comorbidities, respectively. In the main phase, rates, and severity of adverse events (AEs) were similar in riociguat-treated patients across comorbidity subgroups. After 2 years, discontinuations of riociguat due to AEs were also similar across subgroups. Compared with placebo and PDE5i, riociguat improved 6MWD and NT-proBNP across comorbidity groups, and improved WHO-FC and COMPERA 2.0 risk status in patients with 0 or 1–2 comorbidities. CONCLUSIONSRiociguat had an acceptable safety profile in PAH patients with cardiometabolic comorbidities. Efficacy and risk assessment results suggest that riociguat can be beneficial for patients with PAH irrespective of the presence of comorbidities.

Patient factors associated with positive respiratory cultures following tracheostomy in pediatric patients

ObjectivesAn increasing number of pediatric patients undergo tracheostomy placement annually. Despite advances in care, these patients remain at high risk for postoperative complications, including respiratory infections. The risk factors for positive respiratory cultures and the impact of culture positivity on overall morbidity and mortality in this population is not fully characterized. Study design and settingRetrospective cross-sectional analysis of all patients within a single tertiary care institution who underwent tracheostomy placement from January 1, 2019 to 12/31/2021. MethodsWe collected patient demographic information, comorbidities, primary indication for tracheostomy placement, and respiratory culture information preoperatively and postoperatively. The primary outcome measure was positive bacterial respiratory culture with speciation within 1, 3, or 6 months of tracheostomy placement. The secondary outcome measure was all-cause mortality within the study period. ResultsA total of 180 patients with median (IQR) age of 5.2 (3.4–31.0) months at time of tracheostomy placement were included in the study. Nearly half of patients had a positive culture within 1 month (n = 81,47.4 %) while 63.7 % of patients were positive within 6 months of tracheostomy placement (n = 109). Risk factors included respiratory and/or cardiac comorbidities. Positive respiratory cultures within 6 months of surgery and cardiac and/or neurologic comorbidities were associated with increased all-cause mortality following tracheostomy placement. ConclusionsPositive respiratory cultures are common following tracheostomy placement, more so in patients with cardiac and pulmonary comorbid conditions. Positive cultures are associated with increased all-cause mortality. More work is necessary to determine optimal screening frequency and treatment protocols for positive cultures in this population.

Surrogates of Endothelial Injury Predict Survival After Post-transplant Cyclophosphamide

Post-transplant cyclophosphamide (PT-Cy) is becoming the standard of care for preventing graft-versus-host disease (GVHD) following allogeneic hematopoietic stem cell transplant (alloHCT). Cyclophosphamide is associated with endothelial injury. We hypothesized that the endothelial activation and stress index (EASIX) score, being a marker of endothelial dysfunction, will predict non-relapse mortality (NRM) in alloHCT patients receiving PT-Cy for GVHD prophylaxis. We evaluate the prognostic ability of the hematopoietic cell transplantation-specific comorbidity index (HCT-CI) and EASIX scores, and report other factors influencing survival, in patients with hematologic malignancies undergoing alloHCT and receiving PT-Cy-based GVHD prophylaxis. Adult patients with hematologic malignancies who underwent alloHCT and received PT-Cy for GVHD prophylaxis at the three Mayo Clinic locations were included in this study. We retrospectively reviewed the Mayo Clinic database and the available electronic medical records to determine the patient, disease, and transplant characteristics. An HCT-CI score of ≥3 was considered high. The EASIX score was calculated from labs available between day -28 (of alloHCT) to the day of starting conditioning and analyzed on log2 transformed values. A log2-EASIX score ≥2.32 was considered high. The cumulative incidence of NRM was determined using competing risk analysis, with relapse considered as competing risk. Overall survival (OS) from transplant was determined using Kaplan-Meier and log-rank methods. Cox-proportional hazard method was used to evaluate factors impacting survival. A total of 199 patients were evaluated. Patients with a high log2-EASIX score had a significantly higher cumulative incidence of NRM at 1 year after alloHCT (34.5% versus 12.3%, P = .003). Competing risk analysis showed that a high log2-EASIX score (HR 2.92, 95% CI 1.38 to 6.17, P = .005) and pre-alloHCT hypertension (HR 2.15, 95% CI 1.06 to 4.36, P = .034) were independently predictive of 1 year-NRM. Accordingly, we combined the two factors to develop a composite risk model stratifying patients in low, intermediate, and high-risk groups: 111 (55.8%) patients were considered low-risk, 76 (38.2%) were intermediate and 12 (6%) were high-risk. Compared to patients in the low-risk group, the intermediate (HR 2.38, 95% CI 1.31 to 4.33, P = .005) and high-risk (HR 5.77, 95% CI 2.31 to 14.39, P < .001) groups were associated with a significantly inferior 1-year OS. Multiorgan failure (MOF) was among the common causes of NRM (14/32, 43.8%) particularly among patients with prior pulmonary comorbidities [7 (50%) patients]. Our study shows that EASIX score is predictive of survival after PT-Cy. The novel EASIX-HTN composite risk model may stratify patients prior to transplant. MOF is a common cause of NRM in patients receiving PT-Cy, particularly among patients with pulmonary comorbidities.

Overcoming Barriers to Remission in Severe Eosinophilic Asthma: Two-Year Real-World Data With Benralizumab.

Benralizumab has been reported to lead to clinical remission of severe eosinophilic asthma (SEA) at 1 year in some patients. However, whether this is maintained over a longer term remains unclear. Additionally, the impact of pulmonary and extrapulmonary comorbidities on the ability to meet remission is poorly understood. Clinical outcomes including remission of SEA with benralizumab at 1 and 2 years were assessed retrospectively in a real-world UK multi-centre severe asthma cohort. The presence of clinically relevant pulmonary and extrapulmonary comorbidities associated with respiratory symptoms was recorded. Analyses to identify factors associated with the ability to meet remission were performed. In total, 276 patients with SEA treated with benralizumab including 113 patients who had switched from a previous biologic to benralizumab were included. Overall, clinical remission was met in 17% (n = 31/186) and 32% (n = 43/133) of patients at 1 and 2 years, respectively. This increased to 28% at 1 year and 49% at 2 years once patients with pulmonary and/or extrapulmonary comorbidities were excluded. Body mass index (BMI) and maintenance OCS (mOCS) use demonstrated a negative association with clinical remission at 1 (BMI: OR: 0.89, 95% CI: 0.82-0.96, p < 0.01; mOCS: OR: 0.94, 95% CI: 0.89-0.99, p < 0.05) and 2 years (BMI: OR: 0.93, 95% CI: 0.87-0.99, p < 0.05; mOCS: OR: 0.95, 95% CI: 0.89-0.99, p < 0.05). In this long-term, real-world study, patients with SEA demonstrated the ability to meet and sustain clinical remission when treated with benralizumab. The presence of comorbidities including obesity, which are known to be independently associated with respiratory symptoms, reduced the likelihood of meeting clinical remission.

A systematic review of the impact of pulmonary thromboendarterectomy on health-related quality of life.

Pulmonary thromboendarterectomy (PTE) is the current gold standard treatment for chronic thromboembolic pulmonary hypertension (CTEPH) and is a viable treatment option for chronic thromboembolic pulmonary disease (CTEPD). The progressive nature of both diseases severely impacts health-related quality of life (HRQoL) across a variety of domains. This systematic review was performed to evaluate the impact of PTE on short- and long-term HRQoL. A literature search was conducted on PubMed for studies matching the eligibility criteria between January 2000 and September 2022. OVID (MEDLINE), Google Scholar, EBSCOhost (EMBASE), and bibliographies of included studies were reviewed. Inclusion of studies was based on predetermined eligibility criteria. Quality appraisal and data tabulation were performed using predetermined forms. Results were synthesized by narrative review. The structure of this systematic review follows the PRISMA guidelines. This systematic review was prospectively registered in the PROSPERO register (CRD42022342144). Thirteen studies (2184 patients) were included. Within 3 months post-PTE, HRQoL improved in both CTEPD and CTEPH as measured by disease-specific and generic questionnaires. HRQoL improvements were sustained up to 5 years postoperatively in patients with CTEPH post-PTE. PTE remains the gold standard for treating CTEPH and improving HRQoL. Residual pulmonary hypertension and comorbidities such as COPD and coronary artery disease decrement HRQoL over time. The impact of mPAP and PVR on HRQoL outcomes postoperatively remain ambiguous. Pulmonary thromboendarterectomy remains the gold standard for treating CTEPH and has shown to improve HRQoL outcomes at 3-month sustaining improvements up to 5-year postoperatively. Residual pulmonary hypertension and comorbidities hinder HRQoL outcomes post-PTE.

Evaluation of patients with severe pulmonary hypertension and a range of comorbidities prescribed inhaled treprostinil

PurposePatients with pulmonary arterial hypertension (PAH) and additional cardiac or pulmonary comorbidities have a poor prognosis and are frequently excluded from clinical trials. The purpose of this study was to evaluate outcomes of patients with PH secondary to a range of World Symposium on PH (WSPH) groups treated with inhaled treprostinil (iTRE) in a real-world setting. MethodsPatients with PH who were started on treatment with iTRE at Duke University were classified by WSPH Group, and included patients with Group 1, Group 2, Group 3, combined Group 2 & 3 (PH in the setting of left heart failure and chronic lung disease), Group 4, and Group 5 PH. Time to disease worsening, a composite of death, lung transplantation or transition to intravenous prostacyclin, was compared by WSPH Group, and iTRE treatment status using a multivariable Cox proportional hazards model adjusted for age, sex, and REVEAL Lite 2 risk score. Treatment with iTRE was defined as a time-varying covariate. ResultsThe cohort included 270 patients with PH: 30.6% Group 1; 10% Group 2; 32.2% Group 3; 11.1% combined Group 2 & 3; and 15.9% with either Group 4 or 5 PH. At 3-months and 6-months of follow-up, 24.8% and 38.9% of patients respectively were no longer treated with iTRE. Patients who discontinued treatment with iTRE had a significantly higher risk of disease worsening (adjusted HR: 5.02, 95% CI: 3.44 – 7.31). There was no significant difference in disease worsening among WSPH Groups. ConclusionIn a real-world setting, many patients with PH secondary to a range of WSPH Groups tolerated treatment with iTRE. Future studies should phenotype patients with PH based on both comorbidities and therapeutic responsiveness.

Pulmonary comorbidities in people with HIV- the microbiome connection.

To report recent evidence on associations between human microbiome, particularly airway and gut, and pulmonary comorbidities in people with HIV (PWH). Furthermore, we explore how changes in the microbiome may contribute to pulmonary immune dysregulation and higher rates of pulmonary comorbidities among PWH. Finally, we propose future directions in the field. Increased risk of pulmonary comorbidities and rapid lung function decline have been reported in even well treated PWH. Altered microbiota profiles have been reported in PWH with pulmonary comorbidities and rapid lung function decline as compared to those without. The most consistent data have been the association between HIV-related pulmonary comorbidities, lung and oral microbiota dysbiosis, which has been also associated with distinct respiratory mucosal inflammatory profiles and short-term mortality. However, a possible causal link remains to be elucidated. Associations between the lung and oral microbiome, HIV-associated pulmonary comorbidities and rapid lung function decline have been reported in recent studies. Yet the underlying mechanism underpinning the observed associations is largely unknown and substantial knowledge gaps remain. Future research is warranted to unveil the role and mechanism of human microbiome from different anatomical compartments in relation to pulmonary comorbidities in PWH.

Tumor necrosis factor‑α ‑308 G/A genetic polymorphism in patients with chronic obstructive pulmonary disease presenting with hyperactive airways.

Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death worldwide. COPD is often diagnosed late in the disease leading to a delay in management. Notably, tumor necrosis factor-α (TNF-α) polymorphisms may serve an important role in the development of COPD. A single-center, case-control study was conducted to determine the presence of the TNF-α -308 G/A polymorphism among patients diagnosed with COPD presenting with hyperactive airways, patients without COPD presenting with hyperactive airways, and normal study participants without pulmonary comorbidities. Three genotypes: G/G (94%; 157/167), G/A (5%; 9/167) and A/A (1%; 1/167) were detected by quantitative PCR. The present study showed that the presence of the TNF-α -308 G/A polymorphism reduced the odds of having hyperactive airways with COPD by 29.3% and hyperactive airways without COPD by 26.3%. Multinomial logistic regression analysis showed that having the TNF-α -308 G/A polymorphism did not significantly reduce the odds of having hyperactive airways with COPD and without COPD compared to those with the G/G genotype. In conclusion, the presence of the TNF-α -308 G/A gene polymorphism showed no significant association with patients with COPD with or without hyperactive airways. The presence of the TNF-α -308 G/A polymorphism instead had a weak association with the reduction in the development of COPD regardless of the presence or absence of airway hyperactivity.

Pulmonary toxicities in patients (pts) with metastatic breast cancer (mBC) treated with trastuzumab deruxtecan (T-DXd): The Mayo Clinic experience.

11145 Background: T-DXd is increasingly used in mBC. A T-DXd toxicity of special interest is interstitial lung disease/pneumonitis (ILD), occurring in 10-15% of pts in the DESTINY-Breast trials, and with potential lower incidence/severity in earlier line settings [Krop et al, ASCO 2023]. However, in routine practice, T-DXd may be used in pts with more heavily pre-treated mBC and previously exposed to other antibody-drug conjugates (ADC) [Premji et al SABCS 2023]. We evaluated the incidence/severity of T-DXd related ILD in mBC at Mayo Clinic. Methods: We retrospectively identified pts with mBC who received ≥1 dose of T-DXd at Mayo Clinic, Rochester, MN, between July 2022-December 2023. Demographic, mBC, and pulmonary clinical variables were abstracted from the clinical records. Data was summarized using descriptive statistics. Diagnosis of ILD was determined by treating clinicians, and severity to CTCAE V5 based on clinical documentation. Results: 77 pts with mBC received T-DXd during the study period. All were female, the majority (70, 91%) were Caucasian, and median age was 58. 53 (69%) had HER2-low mBC (37 HR+, 16 HR-) and 24 (31%) had HER2+ mBC (17 HR+, 7 HR-). 31 (40%) were active or former smokers. 11 (14%) had pulmonary comorbidities, including 6 (7.8%) with asthma, 2 (2.6%) with prior pneumonitis, and 3 (3.9%) with other pulmonary comorbidities. They had previously received a median of 1 line of endocrine therapy, and 4 lines of chemotherapy, with 20 (26%) having received another ADC. 17 (22%) developed any grade ILD [G1: 3 (4%), G2: 7 (9%), G3: 2 (3%), G4: 1 (1%), G5: 4 (5%)]. Among pts with ILD of any grade, 13 (76.5%) presented with at least 1 symptom (cough/SOB). The median number of T-DXd cycles prior to onset of any grade ILD was 6 (range 2-13), or 18 (range 6-39) weeks. 5 (29%) pts with any grade ILD received a prior ADC. Of pts with ≥G3 ILD (n=7), all were Caucasian, 2 (30%) were prior smokers, none had prior lung disease, and had received a median of 5 prior lines of chemo, with 4 (57%) having received a prior ADC. All grade ≥2 ILDs were treated with systemic steroids, and 1 also received IVIG. CT chest was used for diagnosis of all ILD. 7 pts (41%) required hospitalization, all of whom had bronchoscopy, with 5 (29%) requiring intubation. All pts with G1 ILD (3, 18%) restarted T-DXd without ILD recurrence. Conclusions: In this case series,22% of ps treated with T-DXd experienced ILD (5% G5), higher than the rate observed in the pivotal DESTINY-Breast trials, possibly due to real-world use of T-DXd in more heavily pre-treated pts and in pts with pulmonary comorbidities.

Parietal complications after cystectomy: Incisional and parastomal hernia, epidemiology and risk factors

IntroductionIncisional and parastomal hernias are frequent complications after cystectomy. The aim of our study was to define their incidence, identify risk factors related to the patient and the surgical technique, and identify means of prevention. MaterialThis was a multicenter, retrospective study, analyzing clinical and radiological data from 521 patients operated on for cystectomy between January 2010 and December 2020. ResultsIn total, 521 patients, 471 men and 50 women, mean age 68.8years, were included. Thirty-one patients (6.6%) presented with an evisceration. Risk factors were a history of evisceration (OR: 14.1; 95% CI: [3–66]; P=0.0008), COPD (OR: 3.5; 95% CI: [1.3–9 .4]; P=0.0119), ischemic heart disease (OR: 4; 95% CI: [1. 6–10]; P=0.0036), and split-stitch closure (OR: 3.1; 95% CI: [1.065–8.9]; P=0.0493). Fifty-one patients (9.9%) presented with an incisional hernia. Risk factors were a history of COPD (OR: 4, 95% CI: [2.1–7.6]; P<0.001) and postoperative pulmonary infection (OR: 5.3; 95% CI: [1.05–26.4]; P=0.0079). Seventy-nine patients (15.28%) had a parastomal hernia. Overweight was a risk factor (OR: 2.3; 95% CI: [1.3–4.5]; P=0.0073). ConclusionPatients who are overweight or have pulmonary comorbidities are at greater risk of developing parietal complications after cystectomy. Level of evidenceIII.

Lung Metastasectomy: Where Do We Stand? Results from an Italian Multicentric Prospective Database.

Background/Objectives: The surgical resection of pulmonary metastases is considered a therapeutic option in selected cases. In light of this, we present the results from a national multicenter prospective registry of lung metastasectomy. Methods: This retrospective analysis involves data collected prospectively and consecutively in a national multicentric Italian database, including patients who underwent lung metastasectomy. The primary endpoints were the analysis of morbidity and overall survival (OS), with secondary endpoints focusing on the analysis of potential risk factors affecting both morbidity and OS. Results: A total 470 lung procedures were performed (4 pneumonectomies, 46 lobectomies/bilobectomies, 13 segmentectomies and 407 wedge resections) on 461 patients (258 men and 203 women, mean age of 63.1 years). The majority of patients had metastases from colorectal cancer (45.8%). In most cases (63.6%), patients had only one lung metastasis. A minimally invasive approach was chosen in 143 cases (30.4%). The mean operative time was 118 min, with no reported deaths. Morbidity most frequently consisted of prolonged air leaking and bleeding, but no re-intervention was required. Statistical analysis revealed that morbidity was significantly affected by operative time and pulmonary comorbidities, while OS was significantly affected by disease-free interval (DFI) > 24 months (p = 0.005), epithelial histology (p = 0.001) and colorectal histology (p = 0.004) during univariate analysis. No significant correlation was found between OS and age, gender, surgical approach, surgical extent, surgical device, the number of resected metastases, lesion diameter, the site of lesions and nodal involvement. Multivariate analysis of OS confirmed that only epithelial histology and DFI were risk-factors, with p-values of 0.041 and 0.031, respectively. Conclusions: Lung metastasectomy appears to be a safe procedure, with acceptable morbidity, even with a minimally invasive approach. However, it remains a local treatment of a systemic disease. Therefore, careful attention should be paid to selecting patients who could truly benefit from surgical intervention.

ReDS to detect pulmonary congestion in the emergency department: reproducibility and effect of pulmonary comorbidities

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): This work was supported by the research fund of Bispebjerg University Hospital and Helsefonden. Background Remote Dielectric Sensing (ReDS) is a fast, non-invasive bedside method that estimates lung fluid content observer-independently. We previously described that ReDS has a moderate accuracy to detect acute heart failure in consecutive patients, and we hypothesise that unprecise ReDS estimates may arise from concomitant pulmonary diseases. Still, it is unknown how common comorbidities influence estimates of pulmonary congestion when using ReDS in the emergency department (ED). Purpose To examine the reproducibility of ReDS and the effect of pulmonary comorbidities in dyspnoeic patients in the ED. Method This prospective observational study included consecutive ED patients ≥50 years with acute dyspnoea. Upon admission, all patients were examined with a low-dose chest computed tomography (CT), an echocardiography and a ReDS examination. The default ReDS examination is performed with the ReDS device placed on the right hemithorax in sitting position. However, for reproducibility comparisons, we conducted three ReDS measurements on the right hemithorax after small adjustments, and in supine position (Picture 1: Scenario 1 and 2). Two blinded radiologists evaluated the CT scans for pulmonary congestion and other common pulmonary diseases. Results 97 patients were included and had study examinations conducted within a median of 4.8 hours from admission. Reproducibility comparisons revealed coefficients of variations (CV) of 9.6%, 8.2%, and 8.3% for three ReDS measurements on the right hemithorax (Picture 1: Scenario 1). Similarly, CV was 9.5% for sitting versus supine positions (Picture 1: Scenario 2). For scenario 2, patients with CT verified pulmonary congestion had CV of 5.9%, while those without pulmonary congestion had CV of 10.3%. In multivariate linear regression, we examined the relationship between pulmonary findings on CT and ReDS as a response variable (overall mean ReDS=31.6%, p&amp;lt;0.001). Lower ReDS estimates were observed in patients with pneumonia (-1.81, p=0.215, N=51) and emphysema (-5.44, p=0.001, N=26). Higher ReDS estimates were observed in fibrosis (5.58, p=0.032, N=8) and pulmonary congestion (5.79, p=0.002, N=17). Conclusion ReDS showed good reproducibility for patients with CT verified pulmonary congestion. However, the reproducibility was only moderate for consecutive patients with dyspnoea, who had a high prevalence of CT verified emphysema, lowering the ReDS estimates.Reproducibility comparisons