Pre-existing Lung Disease Research Articles

The optimal antibiotic treatment duration for community-acquired pneumonia in adults diagnosed in general practice in Denmark (CAP-D): an open-label, pragmatic, randomised controlled trial

BackgroundUse of antibiotics is the main driver of antimicrobial resistance which is considered one of the biggest threats to human health. In Denmark, most antibiotics are prescribed in general practice. Acute lower respiratory tract infections, including community-acquired pneumonia (CAP), are among the most frequent indications for antibiotic prescribing. Phenoxymethylpenicillin is established as first-line treatment in general practice in Denmark. However, the treatment duration with phenoxymethylpenicillin is mostly based on traditions. Both 5 and 7 days of treatment is recommended in Danish guidelines, and when asking the general practitioners about what treatment duration, they prescribe the variation is even bigger. Several hospital-based studies have proven short course (≤ 6 days) antibiotic treatment non-inferior to long course (≥ 7 days) treatment of CAP. No evidence exists on the optimal treatment duration for CAP in non-hospitalised patients.This randomised controlled trial aim to investigate the optimal treatment duration with phenoxymethylpenicillin for CAP in adults diagnosed in general practice in Denmark.MethodsThis is an open-label, pragmatic, randomised controlled, five-arm DURATIONS trial. Participants will be recruited from at least 24 general practices in Denmark. Eligible participants are adults, with no pre-existing lung disease, presenting with symptoms of CAP, and in whom the general practitioner finds it relevant to treat with antibiotics. The study will compare treatment with phenoxymethylpenicillin 1.2 MIE q.i.d. in 3, 4, 5, 6, and 7 days.DiscussionThis study will provide evidence for the optimal antibiotic treatment duration of CAP in general practice and inform future guidelines on CAP in all countries using phenoxymethylpenicillin for the treatment of acute respiratory tract infections in adults. The results of this study might also be used to guide treatment recommendations in other countries using phenoxymethylpenicillin.Moreover, a (potential) reduction in antibiotic use might lower the development of antimicrobial resistance, increase patient treatment adherence, reduce risks of adverse events, and lower the economical expTrial registrationClinicalTrials.gov: NCT06295120. Registered 28 February 2024. The Scientific Ethics Committee for the North Denmark Region: N-20230039.

Durvalumab with etoposide and carboplatin for patients with extensive-stage small cell lung cancer and interstitial lung disease: A multicenter, open-label prospective trial

ObjectivesCertain guidelines recommend caution when administering immunotherapy in patients with pre-existing interstitial lung disease (ILD) owing to the high incidence of pneumonitis induced by anti-cancer therapy. A prospective clinical trial assessing the safety of chemoimmunotherapy in patients with small-cell lung cancer (SCLC) and pre-existing ILD is warranted. Therefore, this study evaluated the safety and efficacy of chemoimmunotherapy in patients with extensive-stage (ES)-SCLC and mild idiopathic interstitial pneumonia (IIP). MethodsIn this multicenter prospective trial, patients with ES-SCLC and pre-existing mild chronic fibrosing IIP were recruited. Mild IIP was defined as the exclusion of poor pulmonary function, a definite usual interstitial pneumonia (UIP) pattern, and positivity for autoantibodies in blood tests. The patients received durvalumab, etoposide, and carboplatin every three weeks (induction phase), followed by 1,500 mg durvalumab every four weeks (maintenance phase). The primary endpoint was severe pneumonitis-free rate. ResultsTwenty-one patients were included in the analysis. Among them, 13 patients displayed a probable UIP pattern, whereas eight patients exhibited an indeterminate for UIP pattern. Two patients (9.5 %) had pneumonitis of any grade during the induction phase; one had Grade 1 and the other had Grade 5 pneumonitis. No other patient developed pneumonitis during the maintenance phase. The severe pneumonitis-free rate was 95.2 % (95 % confidence interval (CI): 77.3–99.2 %). The median progression-free survival was 5.5 months (95 % CI: 3.6–6.4 months). Median overall survival was 10.7 months (95 % CI: 6.0 months to not reached). ConclusionsChemoimmunotherapy is a feasible treatment approach for patients with ES-SCLC and mild IIP.

Pulmonary complications post allogeneic haematopoietic stem cell transplant in children.

Haematopoietic stem cell transplant (HCT) is a cellular therapy that, whilst curative for a child's underlying disease, carries significant risk of mortality, including because of pulmonary complications. The aims of this study were to describe the burden of pulmonary complications post-HCT in a cohort of Australian children and identify risk factors for the development of these complications. Patients were identified from the HCT databases at two paediatric transplant centres in Australia. Medical records were reviewed, and demographics, HCT characteristics and pulmonary complications documented. Relative risk ratio was used to identify risk factors for developing pulmonary complications prior to first transplant episode, and survival analysis performed to determine hazard ratio. In total, 243 children underwent transplant during the study period, and pulmonary complications occurred in 48% (117/243) of children. Infectious complications were more common (55%) than non-infective complications (18%) and 26% of patients developed both. Risk factors for the development of pulmonary complications included the following: diagnoses of MPAL (RR 2.16, P = 0.02), matched unrelated donor (RR1.34, P = 0.03), peripheral blood (RR 1.36, P = 0.028) or cord blood (RR 1.73, P = 0.012) as the stem cell source and pre-existing lung disease (RR1.72, P < 0.0001). Children with a post-HCT lung complication had a significantly increased risk of mortality compared with those who did not (HR 3.9, P < 0.0001). This study demonstrates pulmonary complications continue to occur frequently in children post-HCT and contribute significantly to mortality. Highlighting the need for improved strategies to identify patients at risk pre-transplant and enhanced treatments for those who develop lung disease.

4 Treatment Toxicity and Outcomes Following Definitive Radiotherapy for Patients with Early-Stage Non-Small Cell Lung Cancers and Pre-Existing Interstitial Lung Disease: A Systematic Review

4 Treatment Toxicity and Outcomes Following Definitive Radiotherapy for Patients with Early-Stage Non-Small Cell Lung Cancers and Pre-Existing Interstitial Lung Disease: A Systematic Review

Impact of preexisting interstitial lung disease on outcomes of lung cancer surgery: A monocentric retrospective study

IntroductionInterstitial lung disease (ILD) is a known risk factor for lung cancer (LC). However, the surgical risk of LC in patients with ILD remains unclear. Therefore, we conducted a single-center retrospective study to assess clinical features and outcomes of LC population who underwent surgery with or without ILD. MethodsPatients who underwent surgery for LC between January 2006 and June 2023 in our center were assessed using data extracted from the nationwide EPITHOR thoracic surgery database. Suspicion of ILD was based on patients’ records. Confirmation of ILD was then made on the patient's medical and radiological history. Patients were classified according to the pattern of ILD. The study aimed to describe the outcomes after lung cancer resection in patients with confirmed LC-ILD group compared to those without ILD (LC-non-ILD): post-operative complications, disease-free survival (DFS) and overall survival (OS). A subgroup analysis was also performed on patients with idiopathic pulmonary fibrosis and lung cancer (LC-IPF). Results4073 patients underwent surgery for LC at Assistance Publique des Hôpitaux de Marseille between January 2006 and June 2023. Of these, 4030 were in the LC-non-ILD group and 30 were LC-ILD patients. In the LC-ILD group, the predominant CT scan pattern was probable UIP (50 %). OS was not significantly lower in the LC-ILD group (45 months versus 84 months, p = 0.068). Dyspnea and tumor size were identified as potential univariate predictors of OS. No significant differences were observed on post-operative complications or their severity. The most common post-operative complications in the LC-ILD group were prolonged air leak, respiratory failure, or pneumonia. 13 patients had cancer recurrence in the LC-ILD group. ConclusionOur study provides a comprehensive analysis of a LC-ILD population features and outcome when undergoing surgery for LC. Patients with LC-ILD appeared to have a reduced OS compared with LC-non-ILD. Further investigations with larger prospective studies could be useful to confirm and develop these preliminary findings.

Innate and adaptive effector immune drivers of cytomegalovirus disease in lung transplantation: a double-edged sword.

Up to 90% of the global population has been infected with cytomegalovirus (CMV), a herpesvirus that remains latent for the lifetime of the host and drives immune dysregulation. CMV is a critical risk factor for poor outcomes after solid organ transplant, though lung transplant recipients (LTR) carry the highest risk of CMV infection, and CMV-associated comorbidities compared to recipients of other solid organ transplants. Despite potent antivirals, CMV remains a significant driver of chronic lung allograft dysfunction (CLAD), re-transplantation, and death. Moreover, the extended utilization of CMV antiviral prophylaxis is not without adverse effects, often necessitating treatment discontinuation. Thus, there is a critical need to understand the immune response to CMV after lung transplantation. This review identifies key elements of each arm of the CMV immune response and highlights implications for lung allograft tolerance and injury. Specific attention is paid to cellular subsets of adaptive and innate immune cells that are important in the lung during CMV infection and reactivation. The concept of heterologous immune responses is reviewed in depth, including how they form and how they may drive tissue- and allograft-specific immunity. Other important objectives of this review are to detail the emerging role of NK cells in CMV-related outcomes, in addition to discussing perturbations in CMV immune function stemming from pre-existing lung disease. Finally, this review identifies potential mechanisms whereby CMV-directed treatments may alter the cellular immune response within the allograft.

Systemic antibiotics for Pseudomonas aeruginosa infection in outpatients with non-hospitalised exacerbations of pre-existing lung diseases: a randomised clinical trial

BackgroundThe effect of dual systemic antibiotic therapy against Pseudomonas aeruginosa in patients with pre-existing lung disease is unknown. To assess whether dual systemic antibiotics against P. aeruginosa in outpatients with COPD, non-cystic fibrosis (non-CF) bronchiectasis, or asthma can improve outcomes.MethodsMulticenter, randomised, open-label trial conducted at seven respiratory outpatient clinics in Denmark. Outpatients with COPD, non-CF bronchiectasis, or asthma with a current P. aeruginosa-positive lower respiratory tract culture (clinical routine samples obtained based on symptoms of exacerbation not requiring hospitalisation), regardless of prior P. aeruginosa-status, no current need for hospitalisation, and at least two moderate or one hospitalisation-requiring exacerbation within the last year were eligible. Patients were assigned 1:1 to 14 days of dual systemic anti-pseudomonal antibiotics or no antibiotic treatment. Primary outcome was time to prednisolone or antibiotic-requiring exacerbation or death from day 20 to day 365.ResultsThe trial was stopped prematurely based in lack of recruitment during the COVID-19 pandemic, this decision was endorsed by the Data and Safety Monitoring Board. Forty-nine outpatients were included in the study. There was a reduction in risk of the primary outcome in the antibiotic group compared to the control group (HR 0.51 (95%CI 0.27–0.96), p = 0.037). The incidence of admissions with exacerbation within one year was 1.1 (95%CI 0.6–1.7) in the dual antibiotic group vs. 2.9 (95%CI 1.3–4.5) in the control group, p = 0.037.ConclusionsUse of dual systemic antibiotics for 14 days against P. aeruginosa in outpatients with chronic lung diseases and no judged need for hospitalisation, improved clinical outcomes markedly. The main limitation was the premature closure of the trial.Trial RegistrationClinicalTrials.gov, NCT03262142, registration date 2017–08-25.

Risk factors for severe immune-related pneumonitis after nivolumab plus ipilimumab therapy for non-small cell lung cancer.

The efficacy of anti-CTLA-4 antibody (ipilimumab) plus anti-programmed cell death 1 antibody (nivolumab) in treating advanced non-small cell lung cancer (NSCLC) is impeded by an elevated risk of severe immune-related adverse events. However, our understanding of associations among pre-existing fibrosis, emphysematous changes, and objective indicators as predictive factors is limited for severe pneumonitis in NSCLC patients receiving this combination therapy. Thus, we retrospectively investigated these associations, including overall tumor burden, before treatment initiation in the Japanese population. We focused on patients (n = 76) with pre-existing interstitial lung disease (ILD) to identify predictors of severe pneumonitis. Variables included age, sex, smoking status, programmed cell death ligand 1 expression, overall tumor burden, chest computed tomography-confirmed fibrosis, serum markers, and respiratory function test results. Severe pneumonitis was more frequent in patients with squamous cell carcinoma, fibrosis, low diffusing capacity for carbon monoxide (%DLCO), and high surfactant protein D (SP-D) level. Notably, squamous cell carcinoma, baseline %DLCO, and SP-D level were significant risk factors. Our findings revealed the nonsignificance of tumor burden (≥85 mm) in predicting severe pneumonitis, emphasizing the importance of pre-existing ILD. Conversely, in cases without pre-existing fibrosis, severe pneumonitis was not associated with %DLCO or SP-D level (93.2% vs. 91.9%, and 63.3 vs. 40.9 ng/mL, respectively) and was more common in patients with a large overall tumor burden (97.5 vs. 70.0 mm). Vigilant monitoring and early intervention are crucial for patients with squamous cell carcinoma, high SP-D level, or low %DLCO undergoing ipilimumab plus nivolumab therapy.

Remote patient monitoring for early detection of immune checkpoint inhibitor therapy-related pneumonitis in high-risk patients: A pilot-feasibility study.

e13806 Background: Immune checkpoint inhibitor therapy-related (ICI) pneumonitis poses a significant challenge for patients with cancer. It is associated with increased clinical morbidity and mortality, often resulting in prolonged hospital stays and delays and/or discontinuation of cancer-directed treatment. Early detection and prompt treatment of ICI pneumonitis is critical to improve patient outcomes. Therefore, our institution implemented a remote patient monitoring (RPM) program leveraging in-home, electronic health record-integrated technology and virtual centralized nursing to monitor vital signs and patient symptoms in “high-risk” patients treated with immunotherapy. Methods: Patients receiving immunotherapy deemed to be “high-risk” for ICI pneumonitis seen at Mayo Clinic Rochester, Minnesota were offered enrollment in the RPM program beginning in June 2023. High-risk patients included those with pre-existing lung disease (chronic obstructive pulmonary disease, interstitial lung disease); those with a history of resolved ICI pneumonitis being rechallenged with immunotherapy; and those with grade 1 ICI pneumonitis continuing immunotherapy. Eligible patients who agreed to participate in the program were provided a kit consisting of RPM technology and electronic symptom questionnaires. The kit included an armband for continuous vital sign monitoring, a blood pressure monitor, a scale to measure weight, and a pre-connected cellular-enabled tablet for questionnaire answering. RPM data utilized real-time electronic health system integration and predetermined parameters to alert RPM nurses. Pre-specified escalation care pathways were then used to respond and escalate care, as necessary. The primary outcome of this pilot study was to assess the feasibility of implementing an RPM program in this patient population with a secondary outcome to determine the ability to detect ICI pneumonitis before significant clinical symptoms. Results: Sixteen patients were enrolled of whom 5 declined participation (2 due to inconvenience and 3 for unclear reasons) resulting in 11 patients who underwent monitoring. Five patients graduated monitoring without detection of ICI pneumonitis within a 4-month timeframe. Six patients are currently undergoing RPM. 372 alerts occurred of which 8 (2%) were escalated to physician review. These alerts included elevated heart rate in 4, shortness of breath in 3, and elevated blood pressure in 1. One patient was triaged to an emergency department and diagnosed with grade 2 ICI pneumonitis. Conclusions: We show that RPM in patients who are at high-risk for developing ICI pneumonitis can be effectively integrated into a care model and monitor pneumonitis related symptoms. Further studies are needed to prove whether RPM is beneficial in this population including other ICI toxicities.

Endoplasmic reticulum stress-induced senescence in human lung fibroblasts.

Loss of proteostasis and cellular senescence have been previously established as characteristics of aging; however, their interaction in the context of lung aging and potential contributions to aging-associated lung remodeling remains understudied. In this study, we aimed to characterize endoplasmic reticulum (ER) stress response, cellular senescence, and their interaction in relation to extracellular matrix (ECM) production in lung fibroblasts from young (25-45 yr) and old (>60 yr) humans. Fibroblasts from young and old patients without significant preexisting lung disease were exposed to vehicle, MG132, etoposide, or salubrinal. Afterward, cells and cell lysates or supernatants were analyzed for ER stress, cellular senescence, and ECM changes using protein analysis, proliferation assay, and senescence-associated beta-galactosidase (SA-β-Gal) staining. At baseline, fibroblasts from aging individuals showed increased levels of ER stress (ATF6 and PERK), senescence (p21 and McL-1), and ECM marker (COL1A1) compared to those from young individuals. Upon ER stress induction and etoposide exposure, fibroblasts showed an increase in senescence (SA-β-Gal, p21, and Cav-1), ER stress (PERK), and ECM markers (COL1A1 and LUM) compared to vehicle. Additionally, IL-6 and IL-8 levels were increased in the supernatants of MG132- and etoposide-treated fibroblasts, respectively. Finally, the ER stress inhibitor salubrinal decreased the expression of p21 compared to vehicle and MG132 treatments; however, salubrinal inhibited COL1A1 but not p21 expression in MG132-treated fibroblasts. Our study suggests that ER stress response plays an important role in establishment and maintenance of a senescence phenotype in lung fibroblasts and therefore contributes to altered remodeling in the aging lung.NEW & NOTEWORTHY The current study establishes functional links between endoplasmic reticulum (ER) stress and cellular senescence per se in the specific context of aging human lung fibroblasts. Recognizing that the process of aging per se is complex, modulated by the myriad of lifelong and environmental exposures, it is striking to note that chronic ER stress may play a crucial role in the establishment and maintenance of cellular senescence in lung fibroblasts.

P108 Filgotinib for Rheumatoid Arthritis: an observational cohort to assess clinical effectiveness in a single centre

Abstract Background/Aims Filgotinib, a Janus-kinase (JAK) 1 preferential inhibitor, was approved for use in the UK in moderate or severe rheumatoid arthritis (RA) in 2021, as monotherapy or in combination with Methotrexate. Evidence of real-world effectiveness is currently limited. Methods Patients prescribed Filgotinib between December 2021 and August 2022 in NHS Lothian were identified from pharmacy registration data. All underwent clinical efficacy assessment at three months. Electronic patient records (EPR) were reviewed to record baseline data including previous and current treatments. Duration of Filgotinib treatment was recorded, and discontinuation reason if applicable. DAS-28 scores within six months prior to starting Filgotinib were recorded, along with available subsequent scores. Pre-existing interstitial lung disease (ILD), venous thromboembolism (VTE), major adverse cardiovascular events (MACE) and malignancy were recorded, along with incident events during treatment. Results 145 patients were prescribed Filgotinib; 106 (73.1%) females and 39 (26.9%) males, with median age 64 years. Median treatment duration was 447 days. 35 (24.1%) were treated with the reduced 100mg dose. 81 (55.9%) received conventional disease-modifying anti-rheumatic drugs (DMARDs) alongside Filgotinib. 41 (28.3%) patients discontinued treatment: 10 (6.9%) due to loss of effect; 16 (11.0%) due to lack of efficacy; six (4.1%) experienced side effects leading to cessation; five (3.4%) stopped for alternative reasons; one (0.7%) experienced a severe allergic drug reaction; three (2.1%) developed lung cancer and treatment was stopped in each case. 12 (8.3%) patients had ILD prior to treatment. 10 (6.9%) had prior major cardiovascular events, eight (5.5%) had previously treated malignancy, and six (4.1%) had previous VTE. During treatment, 1 (0.7%) patient developed ILD and two (1.4%) developed VTE. There were three (2.1%) new malignancies, all lung cancer. No new MACE occurred. 120 (82.8%) patients were previously treated with biologic or targeted synthetic DMARDs. 59 (40.7%) had failed multiple biologic DMARDs of different classes. 19 (13.1%) switched to Filgotinib from another JAK inhibitor. Pre-treatment DAS-28 scores were recorded in 55 (37.9%) patients with mean 5.1, and during treatment in 44 patients (30.3%) with mean 3.5. 17 (11.7%) patients had DAS-28 recorded both before and during treatment, with pre-treatment mean 5.0 and subsequent mean 2.9. Of these, 10 (58.8%) were classified as a good response by EULAR disease activity criteria, and four (23.5%) as a moderate response. Three (17.6%) were non-responders. Conclusion Our cohort includes 40.7% difficult-to-treat RA. Drug survival as a clinical efficacy surrogate was 71.7% at median duration 447 days, demonstrating patient acceptability and clinical effectiveness. Our service is poor at DAS-28 recording in the EPR, which may partly reflect imaging use at response assessment. Since this cohort was established, the European Medicines Agency has issued guidance advising caution using JAK inhibitors in high-risk groups to minimise the chance of serious side effects. Disclosure C.D. Box: None. S. Ramsay: None. N.D. McKay: Other; N.D.M. has received funding for conference registrations from Abbvie, UCB and Novartis, fees for lecturing from Gilead, and has taken part in advisory board meetings for UCB and Gilead.

Public Health Relevance of US EPA Air Quality Index Activity Recommendations

Reducing exposure to fine particulate matter (<2.5 μm [PM2.5]) air pollution improves cardiopulmonary morbidity and mortality. However, the public health relevance of air quality index (AQI) activity guidelines under present-day environmental conditions in the US has not been critically assessed. To evaluate the public health relevance of following PM2.5 AQI activity guidance in preventing serious atherosclerotic cardiovascular disease (ASCVD) and pulmonary events among adults in the US. This cross-sectional modeling study involved the general adult population and sensitive individuals as designated by the US Environmental Protection Agency (EPA), including adults with preexisting ASCVD or lung disease (asthma or chronic obstructive pulmonary disease). The study was conducted between August 1, 2023, and January 31, 2024. Daily AQI strata for PM2.5 and the corresponding activity recommendations. The main outcome was the number needed to treat (NNT) per day by following activity guidance across daily AQI strata to prevent 1 serious ASCVD or pulmonary event among relevant populations. To calculate PM2.5-induced excess disease event rates per day, estimated baseline disease-specific daily event rates for each group were multiplied by the increase in risks due to PM2.5 levels at each AQI stratum. The number of events prevented per day was calculated by multiplying each excess disease event rate by the percentage in exposure reduction plausibly incurred by following population-specific activity guidance at each AQI level. The NNT is the reciprocal of the number of events prevented. The NNT to prevent ASCVD events was high for the general population and for patients with ASCVD across all AQI strata. The range of values was comparatively lower to prevent pulmonary events among adults with lung disease. During most days (96%) when activity recommendations were promulgated due to elevated PM2.5 (AQI, 101-200), the NNT to prevent a serious disease event remained very high for the general population (>18 million), patients with ASCVD (approximately 1.6-5 million), and adults with lung disease (approximately 66 000-202 000). These findings suggest that existing PM2.5 AQI activity recommendations are of questionable public health relevance in present-day conditions and merit consideration for updating to improve their potential effectiveness.

Gas exchange abnormalities in Long COVID are driven by the alteration of the vascular component.

There are uncertainties whether the impairment of lung diffusing capacity in COVID-19 is due to an alteration in the diffusive conductance of the alveolar membrane (Dm), or an alteration of the alveolar capillary volume (Vc), or a combination of both. The combined measurement DLNO and DLCO diffusion, owing to NO higher affinity and faster reaction rate with haemoglobin compared to CO, enables the simultaneous and rapid determination of both Vc and Dm. The aim of the present study was to better identify the precise cause of post-COVID-19 diffusion impairment. Using the combined NO and CO gas transfer techniques (DLNO and DLCO), it is possible to better understand whether gas exchange abnormalities are due to membrane or alveolar capillary volume components. The present study was aimed at evaluating pulmonary gas exchange one year after severe COVID-19. Results: The cohort included 33 survivors to severe COVID-19 (median age 67 years, 70% male) with no pre-existing lung disease, who underwent clinical, lung function and imaging assessments at 12 months due to persistence of respiratory symptoms or radiological impairment. The gas exchange abnormalities were mainly determined by the compromise of the vascular component as demonstrated by vascular pattern of gas exchange impairment (i.e., DLNO/DLCO≥110%, 76% of the sample), and by a reduction of the Vc (73%), while the Dm was reduced only in 9% of the entire sample. We did not find a correlation between the gas exchange impairment and the extent of the chest CT alterations (DLCO p = 0.059 and DLNO p = 0.054), which on average were found to be mild (11% of the parenchyma). In COVID-19 survivors who are still symptomatic or have minimal CT findings at one year, gas exchange abnormalities are determined by impairment of the vascular component, rather than the diffusive component of the alveolar membrane.

Impact of preexisting interstitial lung disease on mortality in COVID-19 patients from the early pandemic to the delta variant epidemic: a nationwide population-based study

BackgroundCOVID-19 patients with preexisting interstitial lung disease (ILD) were reported to have a high mortality rate; however, this was based on data from the early stages of the pandemic. It is uncertain how their mortality rates have changed with the emergence of new variants of concern as well as the development of COVID-19 vaccines and treatments. It is also unclear whether having ILD still poses a risk factor for mortality. As COVID-19 continues to be a major concern, further research on COVID-19 patients with preexisting ILD is necessary.MethodsWe extracted data on COVID-19 patients between January 2020–August 2021 from a Japanese nationwide insurance claims database and divided them into those with and without preexisting ILD. We investigated all-cause mortality of COVID-19 patients with preexisting ILD in wild-type-, alpha-, and delta-predominant waves, to determine whether preexisting ILD was associated with increased mortality.ResultsOf the 937,758 adult COVID-19 patients, 7,333 (0.8%) had preexisting ILD. The proportion of all COVID-19 patients who had preexisting ILD in the wild-type-, alpha-, and delta-predominant waves was 1.2%, 0.8%, and 0.3%, respectively, and their 60-day mortality was 16.0%, 14.6%, and 7.5%, respectively. The 60-day mortality significantly decreased from the alpha-predominant to delta-predominant waves (difference − 7.1%, 95% confidence intervals (CI) − 9.3% to − 4.9%). In multivariable analysis, preexisting ILD was independently associated with increased mortality in all waves with the wild-type-predominant, odds ratio (OR) 2.10, 95% CI 1.91–2.30, the alpha-predominant wave, OR 2.14, 95% CI 1.84–2.50, and the delta-predominant wave, OR 2.10, 95%CI 1.66–2.66.ConclusionsAll-cause mortality rates for COVID-19 patients with preexisting ILD decreased from the wild-type- to the more recent delta-predominant waves. However, these patients were consistently at higher mortality risk than those without preexisting ILD. We emphasize that careful attention should be given to patients with preexisting ILD despite the change in the COVID-19 environment.

Radiological Diagnosis of Pulmonary Aspergillosis.

Imaging plays an important role in the various forms of Aspergillus-related pulmonary disease. Depending on the immune status of the patient, three forms are described with distinct imaging characteristics: invasive aspergillosis affecting severely immunocompromised patients, chronic pulmonary aspergillosis affecting less severely immunocompromised patients but suffering from a pre-existing structural lung disease, and allergic bronchopulmonary aspergillosis related to respiratory exposure to Aspergillus species in patients with asthma and cystic fibrosis. Computed tomography (CT) has been demonstrated more sensitive and specific than chest radiographs and its use has largely contributed to the diagnosis, follow-up, and evaluation of treatment in each condition. In the last few decades, CT has also been described in the specific context of cystic fibrosis. In this particular clinical setting, magnetic resonance imaging and the recent developments in artificial intelligence have shown promising results.

Prevalence of Cardiovascular Disease and Rate of Major Adverse Cardiovascular Events in Severe Alpha-1 Antitrypsin Deficiency COPD.

Alpha-1 antitrypsin deficiency is an autosomal co-dominant condition that predisposes individuals to early-onset emphysema. As with COPD, AATD-COPD is associated with pulmonary exacerbations, which impacts on overall mortality and quality of life. Though there is evidence that COPD is associated with a higher prevalence of cardiovascular disease and major adverse cardiovascular events (MACE), it is unclear if this is true for patients with AATD-COPD. Prevalence of cardiovascular disease was determined in two separate severe AATD cohorts: AlphaNet, USA and the Birmingham AATD registry, UK. All patients had preexisting lung disease. Cardiovascular disease was defined as presence of any of the following: heart failure, ischaemic heart disease, atrial fibrillation, stroke, and myocardial infarction. A Cox proportional hazards model was used to assess the impact of prior cardiovascular disease and frequent exacerbator phenotype on risk of future MACE. Out of 3493 patients with severe AATD, 14.7% had prior cardiovascular disease, including stroke (2.3%), myocardial infarction (2.2%), and heart failure (2.5%). Frequent exacerbators were more likely to have preexisting cardiovascular disease compared with those with one or no exacerbations in the preceding year (63% vs 44.8%, p = 0.001). There was increased risk of future MACE in frequent exacerbators (HR 1.85, 95% CI 1.24 to 2.75), former and current smokers (HR 1.80, 95% CI 1.07 to 3.02, p = 0.026, and HR 4.04, 95% CI 1.44 to 11.32, p = 0.008, respectively), and those with prior cardiovascular disease (HR 3.81, 95% CI 2.60 to 5.58, p < 0.001). In severe AATD-COPD, MACE are associated with an increased exacerbation frequency, previous cardiovascular disease, and a history of smoking.

Respiratory syncytial virus among hospitalized patients of severe acute respiratory infection in Bhutan: Cross-sectional study.

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections worldwide, particularly in young children. In Bhutan, respiratory disease continues to be among the top 10 diseases of morbidity for several years. This study aimed to estimate the prevalence of RSV among hospitalized patients with severe acute respiratory infection (SARI) in Bhutan. Respiratory specimens were collected from SARI patients of all ages in 2016 and 2018 following influenza surveillance guidelines. Specimens were tested for influenza and RSV, human metapneumovirus, adenovirus, and human parainfluenza virus types 1, 2, and 3 using real-time reverse-transcription polymerase chain reaction assay. Descriptive statistics were used to analyze the result in STATA 16.1. Of the 1339 SARI specimens tested, 34.8% were positive for at least one viral pathogen. RSV was detected in 18.5% of SARI cases, followed by influenza in 13.4% and other respiratory viruses in 3%. The median age of SARI cases was 3 (IQR: 0.8-21 years)years. RSV detection was higher among children aged 0-6 (Adj OR: 3.03; 95% CI: 1.7-5.39) and 7-23 months (Adj OR: 3.01; 95% CI: 1.77-5.12) compared with the children aged 5-15 years. RSV was also associated with breathing difficulty (Adj OR: 1.73; 95% CI: 1.17-2.56) and pre-existing lung disease, including asthma (Adj OR: 2.78; 95% CI: 0.99-7.8). Respiratory viruses were detected in a substantial proportion of SARI hospitalizations in Bhutan.

Current pharmacotherapies for advanced lung cancer with pre-existing interstitial lung disease : A literature review and future perspectives.

Patients with interstitial lung disease (ILD), especially those with idiopathic pulmonary fibrosis, are at increased risk of developing lung cancer (LC). Pharmacotherapy for advanced LC has dramatically progressed in recent years;however, management of LC with pre-existing ILD (LC-ILD) is challenging due to serious concerns about the risk of acute exacerbation of ILD (AE-ILD). As patients with LC-ILD have been excluded from most prospective clinical trials of advanced LC, optimal pharmacotherapy remains to be elucidated. Although the antitumor activity of first-line platinum-based cytotoxic chemotherapy appears to be similar in advanced LC patients with or without ILD, its impact on the survival of patients with LC-ILD is limited. Immune checkpoint inhibitors may hold promise for long-term survival, but many challenges remain, including safety and appropriate patient selection. Further understanding the predictive factors for AE-ILD after receiving pharmacotherapy in LC-ILD may lead to appropriate patient selection and lower treatment risk. The aim of this review was to summarize the current evidence related to pharmacotherapy for advanced LC-ILD and discuss emerging areas of research. J. Med. Invest. 71 : 9-22, February, 2024.

Expert consensus on the management of interstitial lung disease during the COVID-19 epidemic

Expert consensus on the management of interstitial lung disease during the COVID-19 epidemic

The range of haploidentical transplant protocols in sickle cell disease: all haplos are not created equally.

The ideal curative therapy for sickle cell disease (SCD) must be applicable across all ages and include individuals with strokes and preexisting heart, lung, and kidney disease. Myeloablative, matched sibling donor hematopoietic stem cell transplant (HCT) for children with SCD has shown excellent outcomes over the past 3 decades but has been restricted due to the limited availability of a human leukocyte antigen-matched sibling donor (10%-15%) and increased treatment-related death in adults with myeloablative conditioning. To overcome these 2 significant barriers to curative therapy in SCD, related haploidentical HCT has become an active area of research. The use of related haploidentical donors (first- and second-degree relatives) increases the donor pool to at least 90% of those eligible across the life span. Importantly, most adults, even with strokes or significant comorbidities, can tolerate the nonmyeloablative conditioning regimen without treatment-related death. Since 2013, at least 3 related haploidentical HCT strategies have emerged as potential curative therapies for SCD: (1) a nonmyeloablative, T-cell replete, bone marrow transplant with thiotepa and posttransplant cyclophosphamide with a goal of complete donor chimerism; (2) a nonmyeloablative, in vivo T-cell depletion, using peripheral blood stem cells (PBSCs) with a goal of stable mixed donor-recipient chimerism; and (3) a myeloablative, ex vivo T-cell depletion using PBSCs and advanced-technology graft manipulation, with a goal of complete donor chimerism. We review the similarities, differences, outcomes, and gaps in knowledge with these 3 haploidentical HCT approaches for SCD.