Lung Disease Research Articles

Updated systematic review of respiratory health surveillance: what is the evidence and what are the knowledge gaps?

Occupational health surveillance of respiratory disease, if done properly, should contribute to reducing the burden of occupational lung diseases. However, this systematic review shows that the quality and extent of evidence on the effectiveness of occupational health surveillance for respiratory disease is very limited. Therefore, it is essential to expand the evidence base in order to make informed decisions on the need for any changes to established guidance on health surveillance.

Lobar graft evaluation in cadaveric lobar lung redo transplantation after living-donor lobar lung transplantation: a case report

BackgroundLung transplantation is a vital option for patients with end-stage lung disease. However, it faces a significant challenge due to the shortage of compatible donors, which particularly affects individuals with small chest cavities and pediatric patients. The novel approach of cadaveric lobar lung transplantation is a promising solution to alleviate the donor shortage crisis. Both the mid-term and long-term outcomes of lobar lung transplantation are comparable to those of standard lung transplantation. However, patients undergoing lobar lung transplantation reported a significantly higher rate of primary graft dysfunction compared to patients undergoing standard lung transplantation. Therefore, careful donor selection is critical to improve outcomes after lobar transplantation. However, no established method exists to evaluate each lung lobar graft of deceased donors. This case report describes a case of cadaveric lobar lung transplantation to overcome size mismatch and donor shortage, with particular emphasis on lobar graft evaluation.Case presentationA 39-year-old woman with scleroderma-related respiratory failure was listed for deceased donor lung transplantation due to a rapidly progressing disease. Faced with a long waiting list and impending mortality, she underwent bilateral living-donor lobar lung transplantation donated by her relatives. Post-transplant complications included progressive pulmonary vein obstruction and pleural effusion, which ultimately required retransplantation. An oversized donor with pneumonia in the bilateral lower lobes was allocated. Lung ultrasound was used to evaluate each lung lobar graft during procurement. The right upper and middle lobes and left upper lobe were confirmed to be transplantable, and lobar lung redo transplantation was performed. The patient’s post-transplant course was uneventful, and she was discharged home and returned to her daily activities.ConclusionsThis case highlights the clinical impact of cadaveric lobar lung transplantation as a feasible and effective strategy to overcome the shortage of donor lungs, especially in patients with small thoracic cavities. By establishing donor lung evaluation techniques and overcoming anatomical and logistical challenges, cadaveric lobar lung transplantation can significantly expand the donor pool and offer hope to those previously considered ineligible for transplantation.

Emerging Concepts in Bronchiectasis: Diagnosis, Pathophysiology, and Relevance in Lung Disease

This symposium took place during the 2024 European Respiratory Society (ERS) Congress held in Vienna, Austria. The main objective was to discuss the clinical aspects, diagnosis, and pathophysiology of bronchiectasis, a chronic, abnormal dilation of the bronchi, and its association with other lung diseases. The current understanding of the characteristics and prevalence of bronchiectasis in patients with chronic obstructive pulmonary disease (COPD) and alpha 1 antitrypsin (AAT) deficiency was discussed, as well as the relationship between the extent of traction bronchiectasis and exacerbations in idiopathic pulmonary fibrosis (IPF). The overarching message from the symposium was that advances are being made in elucidating the pathophysiology of bronchiectasis, and this is helping clinicians to understand why it occurs in patients with COPD and AAT deficiency. Increased characterisation of bronchiectasis is needed, including the understanding of its aetiology, disease development and progression, and the role of biomarkers in clinical management. This may help to identify treatable traits leading to personalised therapy with anti-inflammatory and antimicrobial drugs in the future.

Longitudinal Micro-Computed Tomography Detects Onset and Progression of Pulmonary Fibrosis in Conditional Nedd4-2 Deficient Mice.

Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease which is usually diagnosed late in advanced stages. Little is known about the subclinical development of IPF. We previously generated a mouse model with conditional Nedd4-2 deficiency (Nedd4-2-/-) that develops IPF-like lung disease. The aim of this study was to characterize the onset and progression of IPF-like lung disease in conditional Nedd4-2-/- mice by longitudinal micro-computed tomography (CT). In vivo micro-CT was performed longitudinally in control and conditional Nedd4-2-/- mice at 1, 2, 3, 4 and 5 months after doxycycline induction. Further, terminal in vivo micro-CT followed by pulmonary function testing and post mortem micro-CT was performed in age-matched mice. Micro-CT images were evaluated for pulmonary fibrosis using an adapted fibrosis scoring system. Histological assessment of lung collagen content was conducted as well. Micro-CT is sensitive to detect onset and progression of pulmonary fibrosis in vivo and to quantify distinct radiological IPF-like features along disease development in conditional Nedd4-2-/- mice. Nonspecific interstitial alterations were detected from 3 months, whereas key features such as honeycombing-like lesions were detected from 4 months onwards. Pulmonary function correlated well with in vivo (r=-0.738) and post mortem (r=-0.633) micro-CT fibrosis scores and collagen content. Longitudinal micro-CT enables in vivo monitoring of onset and progression and detects radiologic key features of IPF-like lung disease in conditional Nedd4-2-/- mice. Our data support micro-CT as sensitive quantitative endpoint for preclinical evaluation of novel antifibrotic strategies.

Saharan dust and respiratory health: Understanding the link between airborne particulate matter and chronic lung diseases (Review).

Saharan dust storms, which originate from the Sahara desert, have a significant impact on global health, especially on respiratory conditions of populations exposed to fine particulate matter that travels across continents. Dust events, characterized by the transport of mineral dust such as quartz and feldspar, lead to the suspension of particulate matter in the atmosphere, capable of traversing long distances and affecting air quality adversely. Emerging research links these dust episodes with increased incidence and exacerbation of lung diseases, including asthma and chronic obstructive pulmonary disease, especially during peak dust emission seasons from November to March. The present review aims to synthesize existing scientific evidence concerning the respiratory health impacts of Saharan dust, examining the environmental dynamics of dust transmission, the physical and chemical properties of dust particles, and their biological effects on human health. Further, it assesses epidemiological studies and discusses public health strategies for mitigating adverse health outcomes. Given the complexity of interactions between atmospheric dust particles and respiratory health, this review also highlights critical research gaps that need attention to better understand and manage the health risks associated with Saharan dust.

Vaccinations in pulmonary diseases - part 2: herpes zoste, RSV, pneumococcal infection and pertussis

RSV is a common cause of respiratory tract infections, posing a risk of severe disease, particularly for newborns and infants, as well as in older individuals with pre-existing conditions. Two safe and effective RSV vaccines were approved in 2023. These vaccines elicit protective antibodies and offer robust protection with no additional benefit from annual boosters. Both vaccines have been approved for individuals aged 60 years and older, while one of the vaccines has also been approved in pregnant women to elicit maternal immunity for passive protection of the unborn child. In Germany, RSV vaccination is currently recommended for all individuals aged 75 years and older, as well as people aged 60-74 years of age with severe underlying conditions. PNEUMOCOCCAL INFECTION: Streptococcus pneumoniae is a primary cause of community-acquired pneumonia (CAP). Since early 2022, a 20-valent conjugate vaccine (PCV20) is approved and recommended for people over 60 years of age and individuals over 18 years of age with risk factors. PCV20 replaces the 23-valent polysaccharide vaccine (PPV23) previously recommended for those over 60 years of age. Although viewed primarily as a childhood disease, the majority of infections affect adults. Patients with chronic respiratory diseases are at a higher risk for severe clinical course of pertussis infection. It has therefore been recommended that all adults should get a pertussis booster with their next scheduled tetanus vaccination, given as a combination vaccine (Tdap). For risk groups (healthcare personnel, community facilities) a booster vaccination every 10 years is recommended. Herpes Zoster (shingles) is caused by the varicella-zoster virus, and reactivations can lead to painful skin lesions and potential complications such as herpes zoster oticus, meningitis, or postherpetic neuralgia. People with chronic lung diseases such as COPD or asthma are at increased risk of herpes zoster-related complications. A recombinant adjuvanted inactivated vaccine was approved in 2018 and offers robust protection against herpes zoster and its complications. The vaccine is recommended for all people over 60 years of age and for certain risk groups over 50 years of age.

Lung MRI: The future is now.

Tomographic imaging via MRI can capture structural abnormalities at high resolution and reveal functional abnormalities if acquired during respiration. In infants and children with chronic lung diseases, MRI can serve as a safe and effective tool to characterize cardiorespiratory disease where PFTs are not feasible. Functional lung imaging via hyperpolarized Xe MRI has been shown to have very high sensitivity to regional airway obstruction, changes in alveolar-airspace size/structure, and gas-exchange due to abnormalities in the interstitium or blood-flow; the technique is routinely used in ages 5 and up. This summary outlines each of the functional measures currently available using Xe MRI.

Quantifying Spatial Distribution of Ventilation Defects in Multiple Pulmonary Diseases With Hyperpolarized 129Xenon MRI.

Hyperpolarized 129Xe MRI assesses lung ventilation, often using the ventilation defect percentage (VDP). Unlike VDP, defect distribution index (DDI) quantifies spatial clustering of defects. To quantify spatial distribution of 129Xe ventilation defects using DDI across pulmonary diseases. Retrospective. Four hundred twenty-one subjects (age = 23.1 ± 17.1, female = 230), comprising healthy controls (N = 60) and subjects with obstructive conditions (asthma [N = 25], bronchiolitis obliterans syndrome [BOS, N = 18], cystic fibrosis [CF, N = 90], lymphangioleiomyomatosis [LAM, N = 50]), restrictive conditions (bleomycin-treated cancer survivors [BLEO, N = 14]; fibrotic lung diseases [FLD, N = 92]), bone marrow transplantation (BMT, N = 53), and bronchopulmonary dysplasia (BPD, N = 19). 3 T, two-dimensional multi-slice gradient echo. Whole-lung mean DDI was extracted from DDI maps; correlated with VDP (percent of pixels <60% of whole-lung mean signal intensity) and pulmonary function tests (PFTs) including FEV1, FVC, and FEV1/FVC. DDI and DDI/VDP, a marker of defect clustering, were compared across diseases. Pearson correlation analysis and Kruskal-Wallis tests. P < 0.0056 for disease groups, P < 0.0125 for categories. DDI was significantly elevated in BMT (8.3 ± 11.5), BOS (30.1 ± 57.5), BPD (16.0 ± 46.8), CF (15.4 ± 27.2), and LAM (12.6 ± 34.2) compared to controls (1.8 ± 3.1). DDI correlated significantly with VDP in all groups (r ≥ 0.56) except BLEO, and with PFTs in CF, FLD, and LAM (r ≥ 0.56). Obstructive groups had significantly higher mean DDI (14.0 ± 32.0) than controls (1.8 ± 3.0) and restrictive groups (4.0 ± 12.0). DDI/VDP was significantly lower in the restrictive group (0.6 ± 0.6) than controls (0.8 ± 0.6) and obstructive group (1.0 ± 1.0). DDI may provide insights into the distribution of ventilation defects across diseases. 3 TECHNICAL EFFICACY: Stage 2.

Outpatient exercise training for chronic lung disease - for whom, how and why?

There is a legal entitlement to participate in outpatient exercise groups in accordance with the German Social Code (Book IX) which regulates and facilitates prescriptions for patients with chronic respiratory diseases. A medical examination with specific inclusion and exclusion criteria prior to admission to an exercise group ensures safe participation.Traditional outpatient exercise groups are conducted in face-to-face groups for 60 to 90 minutes, once a week, with structured warm-up, main and cool-down phases. In addition, since the coronavirus pandemic, the introduction of online exercise groups via videoconferencing has enabled flexible participation (even without a prescription). To date, more than 11,000 German patients have participated in online exercise groups since 2021.Scientific evidence confirms the significant benefits of regular exercise, such as improved physical performance and reduced breathlessness. The psychosocial benefits and the promotion of self-efficacy are additionally supported by the supervision of a specialized trainer. Regular exercise (e.g. in outpatient exercise groups) is an inexpensive and very effective form of therapy to improve the quality of life of people with chronic respiratory diseases.

Contemporary Concise Review 2023: Interstitial lung disease.

In this review, we have discussed several important developments in 2023 in Interstitial Lung Disease (ILD). The association of pollution with genetic predispositions increased the risk of Idiopathic Pulmonary Fibrosis (IPF). An interesting comorbidity of malnutrition was not adequately recognized in ILD. Novel genes have been identified in IPF involving predominantly short telomere length and surfactant protein production leading to alveolar epithelial cell dysfunction. Genetics also predicted progression in IPF. Crosstalk between vascular endothelial cells and fibroblasts in IPF mediated by bone morphogenic protein signalling may be important for remodelling of the lung. A novel modality for monitoring of disease included the 4-min gait speed. New treatment modalities include inhaled pirfenidone, efzofitimod, for sarcoidosis, and earlier use of immunosuppression in connective tissue disease-ILD.

Predictive factors for interstitial lung disease progression in a Singapore systemic sclerosis cohort: a multicentre study.

Interstitial lung disease (ILD) in systemic sclerosis (SSc) is heterogeneous with varied progression rate. This study aimed to identify the baseline clinical characteristics associated with ILD progression within 1, 3 and 5 years of the diagnosis of ILD. This was a prospective, multicentre study - Systematic Sclerosis Cohort Singapore - conducted from January 2008 to February 2021, which included SSc patients with ILD diagnosed by high-resolution computed tomography. Progression of ILD was defined by forced vital capacity (FVC) decline ≥10% predicted or FVC decline 5%-9% predicted, with diffusing lung capacity of carbon monoxide decline ≥15% from the time of ILD diagnosis. Multivariable logistic and Cox regression analyses, adjusting for malignancy and treatment, were performed to determine independent risk factors of ILD progression. Of 124 SSc patients with ILD, 47.6% had limited cutaneous SSc, 33.9% had diffuse SSc and 18.5% had SSc-overlap. Progression of ILD was seen in 6%, 15% and 23% of patients within 1, 3 and 5 years, respectively. After adjusting for malignancy and treatment, anti-La was associated with ILD progression within 1 year (odds ratio [OR] 6.94, 95% confidence interval [CI]: 1.14-42.2; P = 0.04) and 3 years (OR 5.98, 95% CI: 1.31-27.4; P = 0.02), and anti-Scl-70 was associated with ILD progression within 5 years (OR 2.54, 95% CI: 1.05-6.12; P = 0.04). Analysing time to ILD progression as an outcome, anti-La was significantly associated with higher risk of ILD progression (hazard ratio 3.47, 95% CI: 1.18-10.2; P = 0.02). Time to ILD progression was 1.4 years in patients with anti-La versus 6.9 years in patients without anti-La (P = 0.02), and 4.7 years in patients with anti-Scl-70 versus 8.9 years in patients without anti-Scl-70 (P = 0.12). In this Asian cohort of SSc patients, autoantibodies may help to predict ILD progression rates.

High-Flow Nasal Aerosol Therapy; Regional Aerosol Deposition and Airway Responsiveness.

Introduction: In normal subjects, during tidal breathing, aerosols deposit by settling in small airways. With obstructive lung disease (OLD), collapse of airways during expiration causes turbulence and increased deposition in central airways. High-flow nasal cannula (HFNC) therapy, washing out dead space, may affect deposition mechanisms and drug delivery. This study compared aerosol deposition and airway responsiveness in OLD after traditional and HFNC nebulization therapy. Methods: Twelve subjects with moderate to severe OLD participated in a two-day study. Spirometry was measured pre- and post-aerosol inhalation. On Day 1 (D1) subjects tidally inhaled radiolabeled albuterol (99mTc DTPA) by mouth via AeroTech II, (Biodex. Shirley, NY). Day 2 (D2) inhalation was via HFNC using i-AIRE (InspiRx, Inc. Somerset, NJ). The HFNC system (60 L/m) was infused by syringe pump at 50 mL/h. D2 lung deposition was monitored in real time by gamma camera to match D1. Pre and post heart rate, O2 sat, and nasopharyngeal deposition (NP) were measured. Mechanistic contributions were modeled using multiple linear regression (MLR) of deposition rate (DR µg/m) as a function of breathing frequency, airway geometry (FEV1), and parenchymal integrity (DLCO). Results: Albuterol lung depositions were matched (p = 0.13) with D1 central/peripheral (sC/P) ratios 1.99 ± 0.98. Following HFNC, peripheral deposition increased (31% ± 33%, sC/P = 1.51 ± 0.43, p = 0.01). D2/D1% change FVC increased by 16.1 ± 16.7% (p = 0.003). NP deposition averaged 333% of lung. Heart rate and O2 sat were unaffected (p = 0.31, p = 0.63 respectively). DR analysis was markedly different between D1 (R2 = 0.82) and D2 (R2 = 0.12). Conclusion: In subjects with OLD, HFNC nebulization at 60 L/min was well tolerated and increased peripheral drug delivery. Spirometry significantly improved. Systemic effects were undetected indicating limited nasal absorption. MLR demonstrated that different mechanisms of deposition govern traditional vs HFNC aerosol delivery. Breath-enhanced nebulization via HFNC may provide controllable and effective aerosol therapy in OLD.

Giant cell interstitial pneumonia: case series with comprehensive ultrastructural analyses of "not only" hard metal pneumoconiosis.

Giant cell interstitial pneumonia (GIP) is a fibrosing lung disease histologically characterized by centrilobular pulmonary fibrosis and cannibalistic intra-alveolar multinucleated giant cells. It is considered a form of pneumoconiosis caused particularly by secondary exposure to hard metals (cemented carbide or tungsten carbide). Hard metals are commonly used in various industrial applications, such as cutting tools, drilling tools, machine inserts, and other wear-resistant components. However, cases with unknown exposure that recurred in transplanted lungs have been described. This has led to the hypothesis of a complex etiopathogenesis, likely multifactorial, involving the coparticipation of immune mechanisms. We aimed to identify all the elements present in a series of GIP lung samples to better understand the pathogenic mechanisms of the disease. We describe five cases of histologically diagnosed GIP in patients with occupational exposure to metallic dust using ultrastructural characterization to identify metal dust and to quantify asbestos fibres. We found that tungsten was present in three cases, albeit in trace amounts in two of them. Numerous elements were identified in all samples, including asbestos fibres in patients with endstage pulmonary fibrosis. Furthermore, in one of the described cases the recurrence of the disease was also observed in transplanted lungs. These findings support the hypothesis that GIP may be due to elements other than hard metals, with asbestos possibly representing a contributory factor in the expression of a more severe fibrotic disease. The recurrence of GIP observed in transplanted organs strengthens the hypothesis of the existence of a not yet fully understood etiopathogenic immune mechanism.

Betamethasone improved near-term neonatal lamb lung maturation in experimental maternal asthma.

Maternal asthma is associated with increased rates of neonatal lung disease, and fetuses from asthmatic ewes have fewer surfactant-producing cells and lower surfactant-protein B gene (SFTPB) expression than controls. Antenatal betamethasone increases lung surfactant production in preterm babies, and we therefore tested this therapy in experimental maternal asthma. Ewes were sensitised to house dust mite allergen, and an asthmatic phenotype induced by fortnightly allergen lung challenges; controls received saline. Pregnant asthmatic ewes were randomised to receive antenatal saline (asthma) or 12mg intramuscular betamethasone (asthma+beta) at 138 and 139 days of gestation (term=150 days). Lambs were delivered by Caesarean section at 140 days of gestation and ventilated for 45min before tissue collection. Lung function and structure were similar in control lambs (n=16, 11 ewes) and lambs from asthma ewes (n=14, 9 ewes). Dynamic lung compliance was higher in lambs from asthma+beta ewes (n=12, 8 ewes) compared to those from controls (P=0.003) or asthma ewes (P=0.008). Lung expression of surfactant protein genes SFTPA (P=0.048) and SFTPB (P<0.001), but not SFTPC (P=0.177) or SFTPD (P=0.285), was higher in lambs from asthma+beta than those from asthma ewes. Female lambs had higher tidal volume (P=0.007), dynamic lung compliance (P<0.001), and SFTPA (P=0.037) and SFTPB gene expression (P=0.030) than males. These data suggest that betamethasone stimulates lung maturation and function of near-term neonates, even in the absence of impairment by maternal asthma.

Efficacy and tolerance of intravenous methylprednisolone pulses in children with severe bronchopulmonary dysplasia requiring respiratory support.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease that affects premature babies and contributes to their morbidity. French BPD guidelines suggest the use of intravenous methylprednisolone pulses (IVMP) for those who require respiratory support (RS) following 36 weeks postmenstrual age (PMA). However, there is scant data on the efficacy and tolerance for this indication. Our objectives were to assess the efficacy and tolerance of IVMP in patients with severe BPD requiring RS. This retrospective observational study included preterm infants (<32 weeks gestational age) treated by IVMP between January 2016 and March 2021, in a single tertiary care hospital. The primary endpoint was signified by changes in the Pulmonary Severity Score (PSS). Our secondary endpoints were changes in RS and the tolerance of IVMP. Data of 14 children with BPD under RS were reviewed. Their median [IQR] gestational age at birth was (26[26-29.5] weeks). After IVMP administration, the PSS did not improve significantly from baseline day 0 (D0) (0.85[0.55-1.15]) to D7 (0.74 [0.48-1.00]) or Month 1 (1.02 [0.57-1.48]). Three children (21%) experienced a decrease in RS in the following month of IVMP. There was no negative short-term impact on growth. Five infants presented infectious complications. The development quotient was measured in 5 children at 2 years of age. In our study, IVMP did not improve PSS and it was associated with a high number of infections. Other studies are needed to better define the place of IVMP in these infants.

What Is on the Horizon for Treatments in Idiopathic Pulmonary Fibrosis?

Idiopathic pulmonary fibrosis (IPF) is a progressive and often fatal lung disease most commonly encountered in older individuals. Several decades of research have contributed to a better understanding of its pathogenesis, though only two drugs thus far have shown treatment efficacy, i.e., by slowing the decline of lung function. The pathogenesis of IPF remains incompletely understood and involves multiple complex interactions and mechanisms working in tandem or separately to result in unchecked deposition of extracellular matrix components and collagen characteristic of the disease. These mechanisms include aberrant response to injury in the alveolar epithelium, inappropriate communication between epithelial cells and mesenchymal cells, imbalances between oxidative injury and tissue repair, recruitment of inflammatory pathways that induce fibrosis, and cell senescence leading to sustained activation and proliferation of fibroblasts and myofibroblasts. Targeted approaches to each of these mechanistic pathways have led to recent clinical studies evaluating the safety and efficacy of several agents. This review highlights selected concepts in the pathogenesis of IPF as a rationale for understanding current or future therapeutic approaches, followed by a review of several selected agents and their recent or active clinical studies. Current novel therapies include approaches to attenuating or modifying specific cellular or signaling processes in the fibrotic pathway, modifying inflammatory and metabolic derangements, and minimizing inappropriate cell senescence.

Residential fungal β-(1,3)-D-glucan exposure is associated with decreased pulmonary function in fibrotic pulmonary sarcoidosis.

Background: Sarcoidosis is a multi-system disease frequently affecting the lungs. It is thought to be mediated by gene-environment interaction; for example, epidemiological data show organic aerosol exposure increases risk of pulmonary sarcoidosis. Research Question: Does exposure to bioaerosol associate with worse lung disease in patients with pulmonary sarcoidosis? Study Design and Methods: Using an observational, cohort study design, we measured residential exposure to fungal and bacterial cell wall material, β-(1,3)-D-glucan (BDG) and endotoxin, respectively, in healthy control subjects and those with pulmonary sarcoidosis. In the case cohort, we compared bioaerosol concentrations to pulmonary disease severity, assessed by pulmonary function testing, qualitative chest computed tomography (CT), and serum biomarkers. Log-transformed bioaerosol concentrations were compared to lung function and significance and correlation determined by Pearson correlation. Results: Homes of subjects with sarcoidosis had higher BDG and endotoxin concentrations than control subjects. Patients with significant pulmonary fibrosis had greater disease severity (Wasfi severity score, visual analogue scale) and reduced pulmonary function compared to those without fibrosis (all P <0.01). Residential fungal BDG correlated with declining FVC, only in patients with fibrosis on CT imaging ( P =0.02). Survey data revealed higher BDG concentrations were found in homes of cat-owners, and the number of houseplants owned correlated with declines in FVC and FEV 1 ( P =0.05 and 0.02, respectively). In patients without fibrosis, eight inflammatory markers correlated with BDG (6CKine/CCL21, IL-9, IL-17F, IL-21, IL-28A, I-309, MIP-1β, TARC), while in those with pulmonary fibrosis, BDG correlated with two inflammatory markers (Eotaxin-3, M-CSF), suggesting immune anergy to inhaled antigens in patients with fibrosis. Interpretation: In patients with pulmonary fibrosis, disease severity was correlated with residential exposure to fungal cell wall material, but not gram-negative bacterial cell wall material. These patients may experience immune anergy to inhaled antigens.

Assessment of health-related quality of life in individuals with interstitial lung diseases in a tertiary care hospital in south India.

Background & objectives Interstitial lung diseases (ILD) cause progressive symptoms and decline in lung functions which impact health-related quality of life (HRQoL). Although HRQoL is gaining wider acceptance as an endpoint for disease perception, limited data is available regarding the same in Indians with ILD. Hence, this study was undertaken to assess HRQoL and its correlation with lung function parameters in individuals with ILD in a tertiary care setting in south India. Methods A hundred and fifty-nine consecutive patients with ILD were recruited between June 2022 to December 2023. HRQoL was assessed using the ILD specific K-BILD, generic EQ-5D-5L and an adapted version of the validated PESaM questionnaires. Correlation between various domains of the three questionnaires and lung function parameters was analyzed followed by linear regression analysis. Results The study population consisted predominantly of females (64.1%), with CTD-ILD being the most common ILD (40.8%). HRQoL impairment was noted, predominantly affecting the 'breathlessness and activity' domain and significant correlation was noted between K-BILD and EQ-5D-5L across domains. On regression analysis, FVC, 6-minute walk distance and desaturation were independent predictors of HRQoL. Type of ILD and disease duration did not have a significant association with HRQoL measures. Interpretation & conclusions 'Breathlessness and activity' domain of HRQoL was affected the most in participants with ILD. Forced vital capacity, six-minute walk distance and exercise induced desaturation were independent predictors of HRQoL among individuals with ILD.

Environmental and inflammatory factors influencing concurrent gut and lung inflammation.

Crohn's disease and chronic obstructive pulmonary disease (COPD) are chronic inflammatory diseases that affect the gut and lung respectively and can occur comorbidly. Using the SHIP-1-/- model of Crohn's-like ileitis and chronic lung inflammation, the two diseases were co-investigated. Contrary to prior literature, Crohn's-like ileitis was not fully penetrant in SHIP-1-/- mice, and housing in a specific pathogen-free facility was completely protective. Indeed, ileal tissue from SHIP-1-/- mice without overt ileitis was similar to control ilea. However, SHIP-1-/- mice with ileitis exhibited increased granulocytes in ileal tissue together with T cell lymphopenia and they lacked low abundance Bifidobacteria, suggesting this bacterium protects against ileitis. Lung disease, as defined by inflammation in lung washes, emphysema, and lung consolidation, was present in SHIP-1-/- mice regardless of ileitis phenotype; however, there was a shift in the nature of lung inflammation in animals with ileitis, with increased G-CSF and neutrophils, in addition to type 2 cytokines and eosinophils. Deficiency of G-CSF, which protects against lung disease, protected against the development of ileitis in SHIP-1-/- mice. These studies have defined environmental, immune, and inflammatory factors that predispose to ileitis, and have identified that comorbid lung disease correlates with a granulocyte signature.

Lung Ultrasound Assessment of Regional Distribution of Pulmonary Edema and Atelectasis in Infants with Evolving Bronchopulmonary Dysplasia.

Background: Preterm infants are at risk for bronchopulmonary dysplasia (BPD) due to prolonged respiratory support. Studies have described differences in the regional distribution of lung ventilation (non-dependent (NDL) vs. dependent (DL)). The aim of this study was to use LUS to compare regional distribution of pulmonary edema and atelectasis in infants with evolving BPD. Methods: We prospectively performed LUS in premature infants with evolving BPD. On each side, three lung areas (NDL/anterior, lateral, and DL/posterior) were examined for the presence of pulmonary edema and atelectasis. Pulmonary edema scores were assigned based on the number of B-lines, and atelectasis scores were assigned based on the presence/absence of atelectasis. Results: 38 premature infants were enrolled. The NDL showed more pulmonary edema and atelectasis compared to the DL (p = 0.003, p = 0.049, respectively) and compared to the lateral lung (p =< 0.001, p = 0.004, respectively). There was no difference between the lateral and DL (p = 0.188, p = 0.156, respectively). There was no difference between the right and the left lung (p = 0.223, p = 0.656, respectively). Conclusions: In this cohort of preterm infants with evolving BPD, lung disease was unevenly distributed, with more pulmonary edema and atelectasis in the NDL regions compared to the DL or lateral regions.