Abnormal Diffusing Capacity Research Articles

Interferon-signaling pathways are upregulated in people with HIV with abnormal pulmonary diffusing capacity (DL CO ).

People with HIV (PWH) are at greater risk of developing lung diseases even when they are antiretroviral therapy (ART)-adherent and virally suppressed. The most common pulmonary function abnormality in PWH is that of impaired diffusing capacity of the lungs for carbon monoxide (DL CO ), which is an independent risk factor for increased mortality in PWH. Earlier work has identified several plasma biomarkers of inflammation and immune activation to be associated with decreased DL CO . However, the underpinning molecular mechanisms of HIV-associated impaired DL CO are largely unknown. Cross-sectional pilot study with PWH with normal DL CO (values greater than or equal to the lower limit of normal, DL CO ≥ LLN, N = 9) or abnormal DL CO (DL CO < LLN, N = 9). We compared the gene expression levels of over 900 inflammation and immune exhaustion genes in PBMCs from PWH with normal vs. abnormal DL CO using the NanoString technology. We found that 26 genes were differentially expressed in the impaired DL CO group. These genes belong to 4 categories: 1. Nine genes in inflammation and immune activation pathways, 2. seven upregulated genes that are direct targets of the interferon signaling pathway, 3. seven B-cell specific genes that are downregulated, and 4. three miscellaneous genes. These results were corroborated using the bioinformatics tools DAVID (Database for Annotation, Visualization and Integrated Discovery) and GSEA (Gene Sets Enrichment Analysis). The data provides preliminary evidence for the involvement of sustained interferon signaling as a molecular mechanism for impaired DL CO in PWH.

Inflammatory profiles are associated with long COVID up to 6 months after COVID-19 onset: A prospective cohort study of individuals with mild to critical COVID-19.

After initial COVID-19, immune dysregulation may persist and drive post-acute sequelae of COVID-19 (PASC). We described longitudinal trajectories of cytokines in adults up to 6 months following SARS-CoV-2 infection and explored early predictors of PASC. RECoVERED is a prospective cohort of individuals with laboratory-confirmed SARS-CoV-2 infection between May 2020 and June 2021 in Amsterdam, the Netherlands. Serum was collected at weeks 4, 12 and 24 of follow-up. Monthly symptom questionnaires were completed from month 2 after COVID-19 onset onwards; lung diffusion capacity (DLCO) was tested at 6 months. Cytokine concentrations were analysed by human magnetic Luminex screening assay. We used a linear mixed-effects model to study log-concentrations of cytokines over time, assessing their association with socio-demographic and clinical characteristics that were included in the model as fixed effects. 186/349 (53%) participants had ≥2 serum samples and were included in current analyses. Of these, 101/186 (54%: 45/101[45%] female, median age 55 years [IQR = 45-64]) reported PASC at 12 and 24 weeks after COVID-19 onset. We included 37 reference samples (17/37[46%] female, median age 49 years [IQR = 40-56]). In a multivariate model, PASC was associated with raised CRP and abnormal diffusion capacity with raised IL10, IL17, IL6, IP10 and TNFα at 24 weeks. Early (0-4 week) IL-1β and BMI at COVID-19 onset were predictive of PASC at 24 weeks. Our findings indicate that immune dysregulation plays an important role in PASC pathogenesis, especially among individuals with reduced pulmonary function. Early IL-1β shows promise as a predictor of PASC.

Long-term outcomes of pulmonary embolism in children and adolescents

AbstractKnowledge regarding the long-term consequences of pulmonary embolism (PE) in children is limited. This cohort study describes the long-term outcomes of PE in children who were followed-up at a single-center institution using a local protocol that included clinical evaluation, chest imaging, echocardiography, pulmonary function tests, and cardiopulmonary exercise tests at follow-up, starting 3 to 6 months after acute PE. Children objectively diagnosed with PE at age 0 to 18 years, who had ≥6 months of follow-up were included. Study outcomes consisted of PE resolution, PE recurrence, death, and functional outcomes (dyspnea, impaired pulmonary or cardiac function, impaired aerobic capacity, and post-PE syndrome). The frequency of outcomes was compared between patients with/without underlying conditions. In total, 150 patients were included; median age at PE was 16 years (25th-75th percentile, 14-17 years); 61% had underlying conditions. PE did not resolve in 29%, recurrence happened in 9%, and death in 5%. One-third of patients had at least 1 documented abnormal functional finding at follow-up (ventilatory impairments, 31%; impaired aerobic capacity, 31%; dyspnea, 26%; and abnormal diffusing capacity of the lungs to carbon monoxide, 22%). Most abnormalities were transient. When alternative explanations for the impairments were considered, the frequency of post-PE syndrome was lower, ranging between 0.7% and 8.5%. Patients with underlying conditions had significantly higher recurrence, more pulmonary function and ventilatory impairments, and poorer exercise capacity. Exercise intolerance was, in turn, most frequently because of deconditioning than to respiratory or cardiac limitation, highlighting the importance of physical activity promotion in children with PE.

Correlation between chest computed tomography findings and pulmonary function test results in the post-recovery phase of COVID-19.

The radiological and functional lung sequelae in COVID-19 survivors remain unclear. We compared the chest computed tomography findings of COVID-19 patients with normal and abnormal pulmonary function test results in the post-recovery phase. The data of consecutive patients who underwent pulmonary function tests and chest computed tomography within 14 days after recovery from COVID-19 at two medical centers between May and October 2020 were collected retrospectively. Two thoracic radiologists who were blinded to the clinical information and pulmonary function test results classified the patients according to the computed tomography features, evidence of fibrotic-like changes, and semi-quantitative quantification of the extent of pulmonary abnormalities. The clinical characteristics and computed tomography findings of patients with normal pulmonary function test results were compared with those of patients with abnormal results. A total of 101 COVID-19 survivors, comprising 48 ambulatory and 53 hospitalized patients, were included at a median of 95 days from initial symptom onset. Computed tomography revealed fibrotic-like changes in 10.9% of patients. A reduction in the diffusion capacity of carbon monoxide was the most common lung function abnormality (19.8%). Abnormal diffusion capacity of carbon monoxide was associated with the presence and extension of lung opacities on chest computed tomography scans and fibrotic pulmonary abnormalities. The sensitivity, specificity, and accuracy of reduced diffusion capacity of carbon monoxide for detecting fibrotic-like pulmonary changes on chest computed tomography scans were 72.7%, 87.8%, and 86.1%, respectively. Our study suggests that the presence of an abnormal diffusion capacity of carbon monoxide in the post-recovery phase of COVID-19 is associated with a greater risk of long-term parenchymal lung disease, as evidenced by the presence of fibrotic-like changes on chest computed tomography scans, such as traction bronchiectasis and architectural distortion.

Machine Learning and CT Texture Features in Ex-smokers with no CT Evidence of Emphysema and Mildly Abnormal Diffusing Capacity

Ex-smokers without spirometry or CT evidence of chronic obstructive pulmonary disease (COPD) but with mildly abnormal diffusing capacity of the lungs for carbon monoxide (DLCO) are at higher risk of developing COPD. It remains difficult to make clinical management decisions for such ex-smokers without other objective assessments consistent with COPD. Hence, our objective was to develop a machine-learning and CT texture-analysis pipeline to dichotomize ex-smokers with normal and abnormal DLCO (DLCO≥75%pred and DLCO<75%pred). In this retrospective study, 71 ex-smokers (50-85yrs) without COPD underwent spirometry, plethysmography, thoracic CT, and 3He MRI to generate ventilation defect percent (VDP) and apparent diffusion coefficients (ADC). PyRadiomics was utilized to extract 496 CT texture-features; Boruta and principal component analysis were used for feature selection and various models were investigated for classification. Machine-learning classifiers were evaluated using area under the receiver operator characteristic curve (AUC), sensitivity, specificity, and F1-measure. Of 71 ex-smokers without COPD, 29 with mildly abnormal DLCO had significantly different MRI ADC (p<.001), residual-volume to total-lung-capacity ratio (p=.003), St. George's Respiratory Questionnaire (p=.029), and six-minute-walk distance (6MWD) (p<.001), but similar relative area of the lung <-950 Hounsfield-units (RA950) (p=.9) compared to 42 ex-smokers with normal DLCO. Logistic-regression machine-learning mixed-model trained on selected texture-features achieved the best classification accuracy of 87%. All clinical and imaging measurements were outperformed by high-high-pass filter high-gray-level-run-emphasis texture-feature (AUC=0.81), which correlated with DLCO (ρ=-0.29, p=.02), MRI ADC (ρ=0.23, p=.048), and 6MWD (ρ=-0.25, p=.02). In ex-smokers with no CT evidence of emphysema, machine-learning models exclusively trained on CT texture-features accurately classified ex-smokers with abnormal diffusing capacity, outperforming conventional quantitative CT measurements.

Isolated abnormal diffusing capacity for carbon monoxide (iso↓DLco) is associated with increased respiratory symptom burden in people with HIV infection.

An isolated reduction in the diffusing capacity for carbon monoxide (DLco; iso↓DLco) is one of the most common pulmonary function test (PFT) abnormalities in people living with HIV (PWH), but its clinical implications are incompletely understood. In this study, we explored whether iso↓DLco in PWH is associated with a greater respiratory symptom burden. Cross-sectional analysis. We used ATS/ERS compliant PFTs from PWH with normal spirometry (post-bronchodilator FEV1/FVC ≥0.7; FEV1, FVC ≥80% predicted) from the I AM OLD cohort in San Francisco, CA and Seattle, WA, grouped by DLco categorized as normal (DLco ≥lower limit of normal, LLN), mild iso↓DLco (LLN >DLco >60% predicted), and moderate-severe iso↓DLco (DLco ≤60% predicted). We performed multivariable analyses to test for associations between DLco and validated symptom-severity and quality of life questionnaires, including the modified Medical Research Council dyspnea scale (mMRC), the COPD Assessment Test (CAT), and St. George's Respiratory Questionnaire (SGRQ), as well as between DLco and individual CAT symptoms. Mild iso↓DLco was associated only with a significantly higher SGRQ score. Moderate-severe iso↓DLco was associated with significantly higher odds of mMRC ≥2 and significantly higher CAT and SGRQ scores. PWH with moderate-severe iso↓DLco had increased odds of breathlessness, decreased activity, lower confidence leaving home, and less energy. Iso↓DLco is associated with worse respiratory symptom scores, and this association becomes stronger with worsening DLco, suggesting that impaired gas exchange alone has a significant negative impact on the quality of life in PWH. Additional studies are ongoing to understand the etiology of this finding and design appropriate interventions.

Inflammation associated with lung function abnormalities in COVID-19 survivors

BackgroundActivation of inflammatory pathways promotes organ dysfunction in COVID-19. Currently, there are reports describing lung function abnormalities in COVID-19 survivors; however, the biological mechanisms remain unknown. The aim of this study was to analyze the association between serum biomarkers collected during and following hospitalization and pulmonary function in COVID-19 survivors.MethodsPatients recovering from severe COVID-19 were prospectively evaluated. Serum biomarkers were analyzed from admission to hospital, peak during hospitalization, and at the time of discharge. Pulmonary function was measured approximately 6 weeks after discharge.Results100 patients (63% male) were included (age 48 years, SD ± 14) with 85% having at least one comorbidity. Patients with a restrictive spirometry pattern (n = 46) had greater inflammatory biomarkers compared to those with normal spirometry (n = 54) including peak Neutrophil-to-Lymphocyte ratio (NLR) value [9.3 (10.1) vs. 6.5 (6.6), median (IQR), p = 0.027] and NLR at hospital discharge [4.6 (2.9) vs. 3.2 (2.9) p = 0.005] and baseline C-reactive protein value [164.0 (147.0) vs. 106.5 (139.0) mg/dL, p = 0.083). Patients with an abnormal diffusing capacity (n = 35) had increased peak NLR [8.9 (5.9) vs. 5.6 (5.7) mg/L, p = 0.029]; baseline NLR [10.0 (19.0) vs. 4.0 (3.0) pg/ml, p = 0.002] and peak Troponin-T [10.0 (20.0) vs. 5.0 (5.0) pg/ml, p = 0.011] compared to patients with normal diffusing capacity (n = 42). Multivariable linear regression analysis identified predictors of restrictive spirometry and low diffusing capacity, but only accounted for a low degree of variance in pulmonary function outcome.ConclusionOverexpression of inflammatory biomarkers is associated with subsequent lung function abnormalities in patients recovered from severe COVID-19.

Machine operator's lung outbreak due to Eikenella corrodens.

Outbreaks of hypersensitivity pneumonitis (HP) are not uncommon in workplaces where metalworking fluids (MWFs) are used. The recirculation of MWFs leads to microbiological contamination, which is responsible for outbreaks. Most outbreak reports come from USA and the UK; however, no similar reports have been published from Central Europe. To describe an outbreak of MWF-associated HP in workers from a compressor assembly manufacturing facility in Slovak Republic and to identify the potential antigens responsible for the outbreak. We investigated the history of worker's symptoms, physical examinations, lung function tests, radiographic scans and lung biopsies. The MWF samples were analysed for different strains of bacteria and fungi. Antigen extracts were produced from the microorganisms isolated from MWFs, and positive precipitin reactions were evaluated. MWF-associated HP was diagnosed in 21 men and 6 women. All workers had work-related dyspnoea and cough with abnormal pulmonary diffusing capacity. Twenty-four cases had evidence of interstitial lung disease. Four cases were classified as having fibrotic HP. Nineteen microbial isolates (12 bacteria and 7 fungi) were cultured from the MWFs. Twenty-five cases had a positive response to at least one isolate. Eikenella corrodens and Bacillus subtilis were the most frequently reacting antigens (in 15 and 12 workers, respectively). Despite decreasing reports of MWF-associated HP outbreaks over the past several decades, we describe one of the largest outbreaks in Europe. While the bacterium E. corrodens was found in the MWF samples, its relationship to the disease should be further investigated.

Clinical Findings in Adolescents Hospitalized With EVALI; Novel Report on Coagulopathy.

Describe clinical characteristics of adolescents hospitalized with e-cigarette or vaping product use-associated lung injury (EVALI) and to investigate association between EVALI and coagulopathy. We conducted a retrospective cohort study of adolescents admitted to the general inpatient or ICUs at 2 major tertiary children's hospitals from January 2019 to June 2021. We included analysis of demographics, clinical findings, laboratory and imaging results, and outcomes. Forty-four hospitalizations met diagnostic criteria for inclusion per Centers for Disease Control and Prevention guidelines, with 55% of patients admitted after April 2020. Compared with adults, pediatric patients were less likely to present with pulmonary symptoms. Significant laboratory work included elevated white blood cell count of 14.3 k/uL (confidence interval [CI], 13.7-15.0) with neutrophilic predominance, C-reactive protein of 25.2 mg/dL (CI, 22.1-28.2), and erythrocyte sedimentation rate of 66.7 mm/hour (CI, 26.9-76.4). Chest radiographs were poor predictors of disease in 53% of our patients but computed tomography was 100% sensitive. Significant coagulation abnormalities included prothrombin time of 17.7 seconds (CI, 16.4-19.1) and international normalized ratio of 1.54 (CI, 1.43-1.66). Coagulation studies improved with vitamin K and steroid administration. Nine of 16 patients (56%) had abnormal diffusing capacity of the lung for carbon monoxide divided by alveolar volume <80% predicted, suggesting evidence of pulmonary vascular disease, or >100%, suggesting pulmonary hemorrhage. EVALI continues to be an important differential diagnosis in the adolescent population. EVALI is likely a result of systemic inflammation with consequences beyond the pulmonary system. The novel report of coagulopathy among adolescents with EVALI in this cohort reveals an opportunity to detect coagulopathy and initiate early therapy.

Long-Term Effects of COVID-19 on Health Care Workers 1-Year Post-Discharge in Wuhan.

IntroductionTo assess the long-term consequences of coronavirus disease (COVID-19) among health care workers (HCWs) in China (hereafter surviving HCWs).MethodsA total of 303 surviving HCWs were included. Lung (pulmonary function test, 6-min walk test [6MWT], chest CT), physical (St. George’s Respiratory Questionnaire [SGRQ], Modified Medical Research Council dyspnea scale [mMRC], and Borg scale), and psychiatric functions (Essen Trauma Inventory) were evaluated during the 1-year follow-up.ResultsSurviving HCWs had an abnormal diffusion capacity 1 year post-discharge. Participants with a reduced carbon monoxide diffusing capacity (DLCO) comprised 43.48%. The proportion of HCWs with a median 6MWT distance below the lower limit of the normal was 19.4%. An abnormal CT pattern was observed in 37.5% of the HCWs. The SGRQ, mMRC, and Borg scores of surviving HCWs, especially those with critical/severe disease, were significantly higher than those in the normal population. Probable post-traumatic stress disorder (PTSD) was reported in 21.9% of the surviving HCWs. Diffusion capacity impairment was associated with women. Critical/severe illness and nurses were associated with impaired physical function.ConclusionsMost surviving HCWs, especially female HCWs, still had an abnormal diffusion capacity at 1 year. The physical and psychiatric functions of surviving HCWs were significantly worse than those of the healthy population. Long-term follow-up of pulmonary, physical, and psychiatric functions for surviving HCWs is required.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40121-021-00553-0.

Follow-up pulmonary function of COVID-19 patients 4 months after hospital discharge

The end of the acute period of COVID-19 does not mean complete recovery. Observation of patients in the post-COVID-19 period showed that a significant number of people experience shortness of breath, fatigue, muscle weakness, sleep disorders, cough, palpitations, so the term post-COVID-19 syndrome was coined. The examination to identify the causes of complaints of COVID-19 convalescents should include lung function assessment.The aim of the study was to assess the dynamics of lung function 4 months after hospitalization for COVID-19.Methods. 31 patients (26 males, the median age was 49 years) underwent traditional pulmonary function tests (PFTs) (spirometry, body plethysmography, test of diffusing lung capacity) and impulse oscillometry (IOS). Results. During the 1st visit, the average PFTs and IOS parameters were within the normal range in the whole group, apart from the diffusing lung capacity (DLCO), which was reduced mildly (on the border with moderate) in 77% of patients. During the 2nd visit, which was conducted on average 102 days after the 1st one, 58% of patients demonstrated abnormal lung diffusion capacity. The second assessment revealed a statistically significant increase in the slow and forced vital capacity (VC and FVC), the forced exhalation volume in 1 second (FEV1), total lung capacity (TLC), DLCO, and a decrease in the ratio of FEV1/FVC and the residual lung volume to TLC ratio.Conclusion. Post-COVID-19 patients show a statistically significant improvement of their lung function 4 months after hospital discharge. A systematic follow-up is essential for such patients to detect lung function abnormalities and correct them.

Pulmonary Sequelae at 4 Months After COVID-19 Infection: A Single-Centre Experience of a COVID Follow-Up Service.

IntroductionAt the end of the first year of the COVID-19 pandemic, more than 78 million known survivors were recorded. The long-term pulmonary sequelae of COVID-19 remain unknown.MethodsWe performed a retrospective analysis of a post-COVID follow-up service to estimate the burden of persistent pulmonary morbidity in hospitalised COVID survivors.ResultsA total of 221 patients were followed-up: 44 intensive care unit (ICU) and 177 ward patients. Further investigations were planned as per British Thoracic Society Guidelines: For all ICU patients (n = 44) and for 38 of 177 (21%) ward-based patients who had persistent symptoms and/or persistent radiographic changes on CXR at their initial 8-week follow-up visit. In the ward-based cohort, statistically significant associations with persistent symptoms were being an ex- or current smoker, having pre-existing diabetes, and having a longer length of stay. In patients requiring further investigations, pulmonary function tests (PFTs; n = 67) at an average of 15 weeks post-discharge showed abnormalities in at least one PFT parameter in 79% (equating to 24% of the entire cohort). The most common abnormality was an abnormal diffusion capacity of carbon monoxide (TLCO), highest in the ICU cohort (64% ICU vs. 38% non-ICU). TLCO correlated negatively with length of stay and with maximum inspired FiO2 in the patient group as a whole. In ICU patients, TLCO correlated negatively with maximum inspired positive airway pressure. Computed tomography scans (n = 72) at an average of 18 weeks post-discharge showed evidence of persistent ground glass opacities in 44% and fibrosis in 21% (equating to 7% of the entire cohort).ConclusionOur data add to the growing evidence that there will be pulmonary sequelae in a proportion of COVID survivors, providing some insight into what may become a significant chronic global health problem.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-021-01833-4.

Association of lung diffusion capacity with cardiac remodeling and risk of heart failure: The Framingham heart study.

BackgroundLung function abnormalities are ubiquitous in heart failure (HF). It is unclear, however, if abnormal lung diffusion capacity is associated with cardiac remodeling and antedates HF. We hypothesized that lower lung diffusion capacity for carbon monoxide (DLCO) is associated with worse left ventricular (LV) systolic and diastolic function cross-sectionally, and with higher risk of HF prospectively.MethodsWe evaluated 2423 Framingham Study participants (mean age 66 years, 55% women) free of HF who underwent routine echocardiography and pulmonary function tests. We used multivariable regression models to relate DLCO, forced vital capacity (FVC), and forced expiratory volume in 1 second (FEV1) to left ventricular ejection fraction (LVEF), left atrial (LA) emptying fraction (LAEF), E/e’, E/A, LV mass, and LA diameter (LAD). Multivariable-adjusted Cox proportional hazards regression was used to relate DLCO, FEV1, and FVC to incident HF.ResultsIn multivariable-adjusted cross-sectional analyses, DLCO, FEV1, and FVC (dependent variables) were associated positively with LVEF (βDLCO = 0.208, βFEV1 = 0.021, and βFVC = 0.025 per 5% increment in LVEF; p<0.005 for all), and LAEF (βDLCO = 0.707, βFEV1 = 0.058 and βFVC = 0.058 per 5% increment in LAEF; p<0.002 for all). DLCO and FVC were inversely related to E/A (βDLCO = -0.289, βFVC = -0.047 per SD increment in E/A; p<0.001 for all). Additionally, DLCO, FEV1 and FVC were inversely related to HF risk (108 events, median follow-up 9.7 years; multivariable-adjusted hazard ratios per SD increment 0.90, 95% CI 0.86–0.95; 0.42, 95% CI 0.28–0.65, and 0.51, 95% CI 0.36–0.73, respectively). These results remained robust in analyses restricted to non-smokers.ConclusionsOur large community-based observations are consistent with the concept that lower lung diffusion capacity and expiratory flow rates are associated with cardiac remodeling and may antedate HF. Additional studies are needed to confirm our findings and to evaluate the prognostic utility of pulmonary function testing for predicting HF.

Diffusion capacity abnormalities for carbon monoxide in patients with COVID-19 at 3-month follow-up

ObjectiveTo evaluate pulmonary function and clinical symptoms in coronavirus disease 2019 (COVID-19) survivors within 3 months after hospital discharge, and to identify risk factors associated with impaired lung function.Methods and materialCOVID-19 patients were prospectively followed-up with pulmonary function tests and clinical characteristics for 3 months following discharge from a hospital in Wuhan, China between January and February 2020.Results647 patients were included. 87 (13%) patients presented with weakness, 63 (10%) with palpitations and 56 (9%) with dyspnoea. The prevalence of each of the three symptoms were markedly higher in severe patients than nonsevere patients (19% versus 10% for weakness, p=0.003; 14% versus 7% for palpitations, p=0.007; 12% versus 7% for dyspnoea, p=0.014). Results of multivariable regression showed increased odds of ongoing symptoms among severe patients (OR 1.7, 95% CI 1.1–2.6; p=0.026) or patients with longer hospital stays (OR 1.03, 95% CI 1.00–1.05; p=0.041). Pulmonary function test results were available for 81 patients, including 41 nonsevere and 40 severe patients. In this subgroup, 44 (54%) patients manifested abnormal diffusing capacity of the lung for carbon monoxide (DLCO) (68% severe versus 42% nonsevere patients, p=0.019). Chest computed tomography (CT) total severity score >10.5 (OR 10.4, 95% CI 2.5–44.1; p=0.001) on admission and acute respiratory distress syndrome (ARDS) (OR 4.6, 95% CI 1.4–15.5; p=0.014) were significantly associated with impaired DLCO. Pulmonary interstitial damage may be associated with abnormal DLCO.ConclusionPulmonary function, particularly DLCO, declined in COVID-19 survivors. This decrease was associated with total severity score of chest CT >10.5 and ARDS occurrence. Pulmonary interstitial damage might contribute to the imparied DLCO.

A functional macrophage migration inhibitory factor promoter polymorphism is associated with reduced diffusing capacity.

Cigarette smoke exposure is the leading modifiable risk factor for chronic obstructive pulmonary disease (COPD); however, the clinical and pathologic consequences of chronic cigarette smoke exposure are variable among smokers. Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine implicated in the pathogenesis of COPD. Within the promoter of the MIF gene is a functional polymorphism that regulates MIF expression (-794 CATT5-8 microsatellite repeat) ( rs5844572 ). The role of this polymorphim in mediating disease susceptibility to COPD-related traits remains unknown. We performed a cross-sectional analysis of DNA samples from 641 subjects to analyze MIF-794 CATT5-8 ( rs5844572 ) polymorphism by standard methods. We generated multivariable logistic regression models to determine the risk of low expressing MIF alleles for airflow obstruction [defined by forced expiratory volume in 1 s (FEV1)/forced vital capacity ratio <0.70] and an abnormal diffusion capacity [defined by a diffusion capacity for carbon monoxide (DLCO) percent predicted <80%]. We then used generalized linear models to determine the association of MIF genotypes with FEV1 percent predicted and DLCO percent predicted. The MIF-794 CATT5 allele was associated with an abnormal diffusion capacity in two cohorts [odds ratio (OR): 9.31, 95% confidence interval (CI): 1.97-4.06; and OR: 2.21, 95% CI: 1.03-4.75]. Similarly, the MIF-794 CATT5 allele was associated with a reduced DLCO percentage predicted in these two cohorts: 63.5 vs. 70.0 ( P = 0.0023) and 60.1 vs. 65.4 ( P = 0.059). This study suggests an association between a common genetic polymorphism of an endogenous innate immune gene, MIF, with reduced DLCO, an important measurement of COPD severity.

MA 09.04 Increasingly Abnormal Pre-Treatment Diffusion Capacity Is Associated with Greater Local Failure After Lung SBRT

MA 09.04 Increasingly Abnormal Pre-Treatment Diffusion Capacity Is Associated with Greater Local Failure After Lung SBRT

An Association Between Increasingly Abnormal Pretreatment Diffusion Capacity in Medically Inoperable Early Stage Lung Cancer Patients and Increasing Local Failure after Stereotactic Body Radiation Therapy

An Association Between Increasingly Abnormal Pretreatment Diffusion Capacity in Medically Inoperable Early Stage Lung Cancer Patients and Increasing Local Failure after Stereotactic Body Radiation Therapy

Pulmonary function tests findings and their diagnostic value in patients with IgG4-related disease.

IgG4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory disorder that can affect most organs. To date, there have been no detailed assessments of pulmonary function in patients with IgG4-RD. In this study, we investigated pulmonary function in IgG4-RD patients and evaluated the value of pulmonary function tests (PFTs) in diagnosing IgG4-related respiratory disease (IgG4-RRD). This was a retrospective study of 17 patients with IgG4-RD. The patients were divided into two groups: IgG4-RRD group and IgG4-related disease extrapulmonary involvement (IgG4-RDEI) group. The PFT results were compared between the two groups. All patients in the IgG4-RRD group had pulmonary dysfunction. Five of 8 (62.5%) patients in the IgG4-RDEI group had pulmonary dysfunction, despite having normal thoracic computed tomography scans and no respiratory symptoms. Patients in both groups showed restrictive ventilatory dysfunction and abnormal diffusing capacity, and two patients in the IgG4-RRD group had obstructive ventilatory dysfunction. The incidence of diffusing capacity of the lung for carbon monoxide per liter of alveolar volume (DLCO/VA) decrease were significantly higher in the IgG4-RRD group than in the IgG4-RDEI group (P=0.029). DLCO/VA were significantly higher in the IgG4-RDEI than in the IgG4-RRD group (P=0.044), but otherwise, there were no significant differences. We report the first finding of a negative correlation between pulmonary diffusing capacity and total serum concentrations of IgG and IgG subclasses (IgG4, IgG3 and IgG2). DLCO/VA plays an important role for detecting lung involvement in IgG4-RD patients. The patient with high serum IgG may be more prone to respiratory involvement.

Effects on respiratory system due to exposure to wheat flour

BackgroundThere is growing consensus on the deleterious effects of organic dust on respiratory symptoms and function of industrial workers. Flour dust is widely incriminated to cause impairment of lung function. Exposure to flour dust occurs across a range of food industries including grain mills, flour mills and bakeries. Aim of workTo assess the effects of exposure to flour dust on respiratory symptoms and lung function of bakery workers at a number of bakeries in Cairo. Subjects and methodsThe study was conducted on 30 bakery workers working at bakeries in Cairo state, the cases matched for age, sex, and height. All bakery workers participated in this study were subjected to following: Full medical history taking, Thorough clinical examination, Routine laboratory investigation, BMI was calculated, Chest X-ray, Spirometric lung function test, Diffusion capacity for carbon monoxide (DLCO), Further proper radiological assessment using CT scan for cases that show abnormalities in their chest X-ray or DLCOSB. ResultsAll workers included in the study were males. The age of the flour milling workers ranged between 14 and 56years. They worked at least for 10h per day for 6days per week for total working years ranged between 2 and 30years. This study reported that there was an increase in respiratory symptoms among bakery workers due to exposure to wheat flour. Also, 16.6% of the studied population had abnormal spirometry compared to the reference value, 30% had abnormal diffusion capacity of lung to carbon mono-oxide compared to reference value. Nine participants underwent HRCT chest as their DLCOSB has shown diffusion defect, 5 (55.6%) of them have normal HRCT chest and 4 (44.4%) of them have interstitial changes. ConclusionsExposure to wheat flour increases the risk of developing respiratory symptoms; it also causes reduction in the pulmonary function parameters, as regards spirometry and DLCOSB. Exposure to wheat flour causes interstitial lung disease as detected by HRCT chest. Smoking augments the wheat flour induced lung disease.

Correlation of Clinical and Dosimetric Factors With Adverse Pulmonary Outcomes in Children After Lung Irradiation

To identify the incidence and the risk factors for pulmonary toxicity in children treated for cancer with contemporary lung irradiation. We analyzed clinical features, radiographic findings, pulmonary function tests, and dosimetric parameters of children receiving irradiation to the lung fields over a 10-year period. We identified 109 patients (75 male patients). The median age at irradiation was 13.8 years (range, 0.04-20.9 years). The median follow-up period was 3.4 years. The median prescribed radiation dose was 21 Gy (range, 0.4-64.8 Gy). Pulmonary toxic chemotherapy included bleomycin in 58.7% of patients and cyclophosphamide in 83.5%. The following pulmonary outcomes were identified and the 5-year cumulative incidence after irradiation was determined: pneumonitis, 6%; chronic cough, 10%; pneumonia, 35%; dyspnea, 11%; supplemental oxygen requirement, 2%; radiographic interstitial lung disease, 40%; and chest wall deformity, 12%. One patient died of progressive respiratory failure. Post-irradiation pulmonary function tests available from 44 patients showed evidence of obstructive lung disease (25%), restrictive disease (11%), hyperinflation (32%), and abnormal diffusion capacity (12%). Thoracic surgery, bleomycin, age, mean lung irradiation dose (MLD), maximum lung dose, prescribed dose, and dosimetric parameters between V22 (volume of lung exposed to a radiation dose ≥22 Gy) and V30 (volume of lung exposed to a radiation dose ≥30 Gy) were significant for the development of adverse pulmonary outcomes on univariate analysis. MLD, maximum lung dose, and Vdose (percentage of volume of lung receiving the threshold dose or greater) were highly correlated. On multivariate analysis, MLD was the sole significant predictor of adverse pulmonary outcome (P=.01). Significant pulmonary dysfunction occurs in children receiving lung irradiation by contemporary techniques. MLD rather than prescribed dose should be used to perform risk stratification of patients receiving lung irradiation.