Significant Impairment Of Lung Function Research Articles

Impact of post-COVID-19 lung damage on pulmonary function, exercise tolerance and quality of life in Indian subjects.

After recovery from COVID-19, there is data to suggest potential long-term pulmonary sequelae and associated impairment of functional capacity. This cross-sectional study was designed to assess the impact on respiratory function in a cohort of Indian subjects. Subjects who had recovered from COVID-19 were recruited. Clinical symptoms, pulmonary function test results, 6-minute walk test (6MWT) results, St George's Respiratory questionnaire (SGRQ) and chest radiographs were obtained. Information on the COVID-19 illness during hospitalization, baseline laboratory biomarkers and the disease severity categories as outlined by WHO (asymptomatic, mild, moderate, severe and critical), were retrieved from the hospital records. The 'COVID pneumonia'(WHO category moderate, severe & critical) group was compared with the 'Mild COVID' (WHO category mild) group and likewise, the WHO category moderate and the WHO category severe/critical groups were compared. In 207 subjects, whose mean age was 48.7 years were assessed after an average of 63 days from onset of symptom, 35% had TLC< 80% (restrictive defect), 8.3% had FEV1/FVC<70% (obstructive defect) and 44.4% had diminished DLCO<80% (diffusing capacity). The 'COVID-19 pneumonia' group when compared to the 'mild COVID-19' group, had lower FVC% (77.85 VS 88.18; P = 0.001), TLC% (79.48 VS 87.91; P = 0.0002), DLCO% (75.30 VS 89.20; P<0.0001) and DLCO/VA% (105.6 VS 111.8; P = 0.032), decreased minimum oxygen saturation (94.89 VS 97.73; P<0.0001) and more subjects had a drop in saturation of ≥ 4% (21.69% VS 4.84%; P = 0.001) during the 6MWT, and a greater mean total SGRQ score (29.2 VS 11.0; P<0.0001). To our knowledge, this is the first such report on Indian subjects. We have shown that post-COVID-19 lung damage leads to significant impairment of lung function, quality of life and effort tolerance.

Alpha-defensins inhibit ERK/STAT3 signaling during monocyte-macrophage differentiation and impede macrophage function

Alpha-1-antitrypsin deficiency (AATD) is a genetic disorder associated with a 5–tenfold decrease in lung levels of alpha-1-antitrypsin (AAT) and an increased risk for obstructive lung disease. α-defensins are cationic broad-spectrum cytotoxic and pro-inflammatory peptides found in the azurophilic granules of neutrophils. The concentration of α-defensins is less than 30 nM in the bronchoalveolar lavage fluid of healthy controls but is up to 6 μM in AATD individuals with significant lung function impairment. Alveolar macrophages are generally classified into pro-inflammatory (M1) or anti-inflammatory (M2) subsets that play distinct roles in the initiation and resolution of inflammation. Therefore, monocyte-macrophage differentiation should be tightly controlled to maintain lung integrity. In this study, we determined the effect of α-defensins on monocyte-macrophage differentiation and identified the molecular mechanism of this effect. The results of this study demonstrate that 2.5 μM of α-defensins inhibit the phosphorylation of ERK1/2 and STAT3 and suppress the expression of M2 macrophage markers, CD163 and CD206. In addition, a scratch assay shows that the high concentration of α-defensins inhibits cell movement by ~ 50%, and the phagocytosis assay using flow cytometry shows that α-defensins significantly reduce the bacterial phagocytosis rate of monocyte-derived macrophages (MDMs). To examine whether exogenous AAT is able to alleviate the inhibitory effect of α-defensins on macrophage function, we incubated MDMs with AAT prior to α-defensin treatment and demonstrate that AAT improves the migratory ability and phagocytic ability of MDMs compared with MDMs incubated only with α-defensins. Taken together, this study suggests that a high concentration of α-defensins inhibits the activation of ERK/STAT3 signaling, negatively regulates the expression of M2 macrophage markers, and impairs innate immune function of macrophages.

Diagnóstico tardio de fibrose cística em criança com teste de triagem neonatal negativo

Cystic fibrosis (CF) is an autosomal recessive genetic disease in which CFTR (cystic fibrosis transmembrane conductance regulator) gene dysfunction, related to the transmembrane chlorine movement. This leads to the production of thicker secretions that occlude the light of the involved structures, causing inflammation and compromising the function of the affected organs. The respiratory and digestive systems are the main affected by this pathology, generating growth deficits, chronic respiratory infections, progressive damage to the lung tissue. Because it is a multisystem disease, early treatment aided by the screening test showed a better outcome when compared to treatment initiated after late diagnosis. The various neonatal screening tests (TTN) for cystic fibrosis have high sensitivity and specificity, but false positives and false negatives may occur. In this case report, we describe a preschooler who had a negative neonatal screening test and his diagnosis occurred after 2 years of age in the investigation of a hepatomegaly. However, the child presented pulmonary symptoms from the first days of life that were being treated as bronchial hyperresponsiveness and, later, as asthma. In the diagnostic investigation, the first dosage of chlorine in sweat has already shown significant elevation. Enzymatic treatment was started with slow and progressive improvement of respiratory symptoms. And although the child responded to the start of treatment, it already had significant impairment of lung function. Thus, although TTN for cystic fibrosis has high sensitivity, it does not replace sweat chlorine dosage in children with very suggestive symptoms.

Spirometric abnormalities following treatment for pulmonary tuberculosis in Ilorin, Nigeria.

Pulmonary tuberculosis (PTB) contributes significantly to morbidity and mortality worldwide, and despite microbiological cure for the disease, many patients still demonstrate residual respiratory symptoms and spirometric abnormalities. The study aimed at identifying the prevalence, pattern and factors associated with spirometric abnormalities in patients successfully treated for PTB in Ilorin, Nigeria. This was a hospital-based cross-sectional study at the pulmonary outpatient clinics of the University of Ilorin Teaching Hospital and Kwara State Specialist Hospital, Sobi, Ilorin. A total of 308 consenting patients who had been certified microbiologically cured for bacteriologically confirmed PTB in the preceding 3 years had assessment of residual pulmonary symptoms, spirometry and plain chest radiograph. The prevalence of abnormal spirometry following treatment for PTB was 72.1% (confidence interval: 0.6682-0.7695), with restrictive pattern being the predominant abnormality (42.2%). Over half of the patients (56.5%) had at least one residual respiratory symptom. The significant predictors of abnormal spirometry were PTB retreatment (adjusted odds ratio [aOR] = 6.918; P = 0.012), increasing modified Medical Research Council dyspnoea scores (aOR = 7.935; P = 0.008) and increasing radiologic scores (aOR = 4.679; P ≤ 0.001) after treatment. There is significant residual lung function impairment in majority of the individuals successfully treated for PTB in Ilorin. This highlights the need for spirometric assessment and follow-up after treatment.

DOZ047.28: Clinical utility of cardiopulmonary exercise testing in children with esophageal atresia

Abstract Background Respiratory morbidity in children with esophageal atresia/tracheoesophageal fistula (OA/TOF), due to impaired mucociliary clearance, recurrent infections, and aspiration, may impair pulmonary function during childhood and this may persist into adult life. Early recognition of reduced lung function could optimize respiratory management and improve long-term outcomes. However, static lung function assessments, using spirometry and body plethysmography, may not sensitively identify impaired lung function. Cardiopulmonary exercise testing (CPET), which involves a dynamic assessment of respiratory function and determines aerobic capacity, degree of fitness, and ventilatory (breathing) reserve during maximal exertion, may detect poor lung function earlier. Aim This study determines the clinical utility of cardiopulmonary exercise testing in children with OA/TOF. Methods Retrospective chart review of children attending a multidisciplinary OA/TOF clinic who underwent spirometry, plethysmography, and a maximal CPET (Bruce Treadmill Protocol). Plethysmography and CPET were performed on the same day in 16 children; 4 children within 2 days and 6 within 2 months. Studies exceeding 2 months were not analyzed (n = 2). Results Thirty-nine children, aged ≥ 7 years, underwent CPET when clinically well. Thirty-two children, 7–18 years, achieved a maximal CPET (82.1%). There was no significant exercise-induced drop in PPFEV1 in any child. One child experienced a reduction in oxygen saturation to 92%. Exercise capacity (VO2MAX, peak oxygen consumption) was normal in 30 children (93.8%). However reduced ventilatory or breathing reserve (BR), defined as &lt;20% predicted, was identified in 18 children (56.3%). Four of these children had no ventilatory reserve (BR = 0). In contrast, spirometry was normal in 20 children (62.5%). Nine (28%) had a mild obstructive or restrictive pattern. One child had moderate restriction and 2 had a mixed pattern. Plethysmography (n = 26) revealed mild restrictive lung disease in 9 (34.6%). An additional 3 children had air-trapping. Conclusion Children with OA/TOF have significant lung function impairment. Spirometry and plethysmography revealed normal or mildly abnormal airway function/lung volumes in the majority of children. CPET identified significant ventilation limitation in over half of all children. CPET assessment is a feasible and sensitive assessment of cardiorespiratory function in children with OA/TOF. Further evaluation of risk factors and longitudinal CPET assessments may inform future management guidelines.

Lung function growth trajectories in non-asthmatic children aged 4–9 in relation to prenatal exposure to airborne particulate matter and polycyclic aromatic hydrocarbons – Krakow birth cohort study

BackgroundPatterns of lung function development during childhood can be helpful in understanding the pathogenesis of respiratory diseases. A variety of environmental and lifestyle factors, present from the prenatal period to adulthood, may affect or modulate lung function growth. The aim of this study was to investigate, the associations between individual growth trajectories of children's lung function during childhood and prenatal exposure to airborne fine particulate matter (PM2.5) and polycyclic aromatic hydrocarbons (PAH), which were hypothesized to adversely affect spirometry parameters. Material and methodsThe study group comprised 294 non-asthmatic, full term children from the Krakow birth cohort, who underwent annual spirometry testing at the ages of 4–9 years. Individual personal air monitoring of PM2.5 and PAH were performed over 48 h in the second trimester of pregnancy. Possible confounders or modifiers such as child's gender, height, atopic status and exposure to environmental tobacco smoke (ETS) were considered. Polynomial multilevel mixed models were used to assess the growth rates of children's lung functions. ResultsLung function trajectories differed significantly for boys and girls for FVC, FEV1 and FEF25–75. Girls had lower rates of increase than boys: − 20.5 (95%CI: − 32.4; − 8.6) ml/year (FVC); − 19.9 (95%CI: −30.7;−9.0) ml/year (FEV1); and − 32.5 (95%CI: − 56.9; − 8.2) ml/year (FEF25–75). Spirometry functions increased with age; however the growth rate decelerated over time. Significant lung function impairment (lower FVC and FEV1 levels) was observed from 4 to 9 years among subjects prenatally exposed to higher levels of PM2.5 as well as PAH, but not in the case of FEF25-75. No significant differences were observed in the rates of increase over time in relation to prenatal PM2.5 and PAH exposure. ConclusionOur results indicate that in non-asthmatic children high prenatal exposure to airborne PM2.5 and PAH is associated with lower trajectories of FVC and FEV1, but not the rate of increase over time, suggesting that the initial effect is not diminishing in time.

Combined Effects of in Utero and Adolescent Tobacco Smoke Exposure on Lung Function in C57Bl/6J Mice.

Background:Fetal determinants of airway function, such as in utero exposure to maternal cigarette smoke (CS), may create a predisposition to adult airflow obstruction and chronic obstructive pulmonary disease (COPD) in adulthood. It has been suggested that active smoking in adolescence and preexisting airflow obstruction have synergistic deleterious effects.Objective:We used a mouse model to investigate whether there is a synergistic effect of exposure to CS in utero and during adolescence on lung function.Methods:Female C57Bl/6J mice were exposed to CS or to filtered room air during pregnancy. Exposure to CS began 2 weeks before mating and continued until delivery. After birth, the pups were not exposed to CS until day 21 (D21). Between D21 and D49, corresponding to “adolescence,” litters were randomized for an additional 4 weeks of exposure to CS. Lung morphometry, lung mechanics, and the expression of genes involved in senescence were evaluated in different subsets of mice on D21 and D49.Results:In utero exposure to CS induced significant lung function impairment by D21. CS exposure between D21 and D49 induced significant functional impairment only in mice exposed to CS prenatally. On D49, no difference was observed between subgroups in terms of lung p53, p16, p21, and Bax mRNA levels.Conclusions:Our findings suggest that prenatal and adolescent CS exposure have a synergistic effect on lung function in mice. The combined effect did not appear to be a consequence of early pulmonary senescence.Citation:Drummond D, Baravalle-Einaudi M, Lezmi G, Vibhushan S, Franco-Montoya ML, Hadchouel A, Boczkowski J, Delacourt C. 2017. Combined effects of in utero and adolescent tobacco smoke exposure on lung function in C57Bl/6J mice. Environ Health Perspect 125:392–399; http://dx.doi.org/10.1289/EHP54

Dramatic improvement of anti-SS-A/Ro-associated interstitial lung disease after immunosuppressive treatment

The aim of the study was to report three patients affected by interstitial lung disease associated with positive anti-SS-A/Ro autoantibody who showed a dramatic improvement after immunosuppressive treatment. Medical charts were reviewed to obtain clinical data, laboratory parameters, lung function tests, high-resolution computed tomography results and response to immunosuppressive treatment. The three patients showed a clinical picture of a lung-dominant connective tissue disease characterized by a sudden onset with dyspnea, cough and subtle extrathoracic features together with positive anti-SS-A/Ro antibody and weak titer antinuclear antibodies. All three patients responded favorably to immunosuppressive therapy: Two cases were treated with a combination of corticosteroid and cyclophosphamide followed by mycophenolate mofetil; in the third patient, clinical benefit was obtained after rituximab was added to corticosteroid and immunosuppressant drug. In spite of an abrupt onset with significant lung function impairment, all three patients had a favorable clinical response to immunosuppressive therapy. This report may be useful in making therapeutic decisions in case of interstitial lung disease associated with anti-SS-A antibody.

Immunologic measurement of elastin-derived peptides in human serum.

Chronic obstructive pulmonary disease (COPD), a major cause of morbidity and death in the smoking population, develops insidiously over many years, and usually significant impairment of lung function has occurred before the disease is diagnosed. It is likely that destruction of the elastic fiber is a prerequisite for the development of the disease, and it is possible that immunologic identification in the serum of peptides derived from lung elastin degradation might be an effective approach to the early detection and monitoring of the disease. We prepared antibodies to peptides derived from human lung parenchymal elastin and used these antibodies in an enzyme-linked immunosorbant assay to quantitate elastin-derived peptides in the serum of 39 normal control nonsmokers, 33 smokers with normal lung function, and 40 patients with COPD. On average, statistically significant higher levels of elastin-derived peptides were found in the normal smokers and COPD patients compared to the controls. Further work with larger numbers of subjects is necessary to determine whether such a test is effective in identifying those individuals who are at risk of developing COPD.

Utilization of a peroxidase antiperoxidase complex in an enzyme-linked immunosorbent assay of elastin-derived peptides in human plasma.

Chronic obstructive pulmonary disease (COPD), a major cause of morbidity and death in the smoking population, develops insidiously over many years, and significant impairment of lung function usually occurs before the disease is diagnosed. Because lung elastin degradation appears to be a prerequisite for the development of the disease, immunologic detection of elastin-derived peptides in the blood might be an effective approach to the early detection and monitoring of the disease. We here report an improved enzyme-linked immunosorbent assay for elastin peptides using a peroxidase-antiperoxidase complex as the reporter group. The assay is sensitive to 2 ng/ml elastin peptides. We show that for optimal, reproducible results the assay should be carried out at 16 degrees C rather than at room temperature and that determinations should be made on plasma containing protease inhibitors rather than on serum. The levels of elastin-derived peptides appeared to remain relatively constant when multiple samples were taken during a 5- to 10-wk period from individual subjects. In addition, patients with COPD had elevated elastin peptide levels (127 +/- 47 ng/ml) compared with levels in normal nonsmokers (58 +/- 17 ng/ml), whereas normal smokers had values intermediate between the 2 groups (mean peptide levels of 76 +/- 42 ng/ml). A small group of normal smokers (20%) had elevated elastin peptide levels similar to those in the emphysema group and may represent that group of smokers who are at risk of developing obstructive lung disease.

Impact of left ventricular late enhancement on pulmonary arterial hypertension in idiopathic dilated cardiomyopathy

Methods 71 consecutive patients (p) with DCM, left ventricular systolic dysfunction (LVEF<35%) and normal coronary angiography followed in an outpatient HF clinic, were prospectively enrolled in two institutions. All p had to be in stable clinical condition in the last month. Exclusion criteria were: contraindications for contrast-enhanced cardiac MR (ce-CMR), significant impairment of lung function by clinical criteria or spirometry and history of thromboembolic disease. All patients underwent ECG, echo, blood test and a ce-CMR study in a Philips Intera ® 1.5 T scanner, which included cine imaging, phase contrast in the main pulmonary artery and aorta and late enhancement (LE). Postprocessing was performed with QMASS 7.2 ® (Medis, The Netherlands). PVR was calculated following the equation: 19.38 -(4.62*Ln pulmonary artery average velocity) (0.08 x RVEF %)

Lung function trajectories from birth through puberty reflect asthma phenotypes with allergic comorbidity

Childhood asthma phenotypes reflecting underlying developmental mechanisms are sought, with little information on asthma phenotypes based on allergic comorbidities. We asked whether lung function trajectories from birth to 16 years were associated with asthma phenotypes with comorbid allergic rhinitis and atopic dermatitis. Lung function (given as z scores) was measured at birth in 329 subjects in the "Environment and Childhood Asthma" birth cohort study in Oslo by using tidal flow volume loops, and at 10 and 16 years by using spirometry. Asthma phenotypes were classified on the basis of recurrent bronchial obstruction at 0 to 2 years, and asthma from the 2- to 10-year and 10- to 16-year intervals, and by combining asthma, atopic dermatitis, and/or allergic rhinitis from 10 to 16 years, stratifying for allergic sensitization. The reference group included 231 subjects without recurrent bronchial obstruction or asthma. Lung function trajectories differed significantly for asthma comorbidity phenotypes for FEV1, forced expiratory flow at 25% to 75% of forced vital capacity, and FEV1/forced vital capacity (all P < .0001). Significant lung function impairment was observed from birth through 16 years among subjects with asthma, atopic dermatitis, and allergic rhinitis. Lung function trajectories in subjects with asthma at 10 to 16 years or asthma in remission differed significantly for all 3 spirometric values compared with the trajectories in those who never had asthma (P < .0001), but not between asthma groups. Allergic sensitization was not significantly associated with asthma phenotype lung function trajectories. The trajectory consisting of impaired lung function from birth throughout childhood in children with asthma, atopic dermatitis, and allergic rhinitis appears less likely to be driven by allergic sensitization, and may imply disease onset in utero, with clinical presentation later in childhood.

Chryseobacterium spp., ¿nuevo patógeno oportunista asociado a fibrosis quística?

IntroductionThere is an increase in the isolation of non-fermenting gramnegative bacilli in patients with cystic fibrosis (CF). The present study evaluates the frequency of isolates of Chryseobacterium spp., analyzing its characteristics, resistance patterns and clinical outcome of patients. MethodsIt has been collected all respiratory isolates of Chryseobacterium spp. of patients attended in the CF unit of Hospital de la Princesa for three years (march 2009-march 2012). For phenotypic and genotypic identification and sensitivity study conventional methodology was used. For the assessment of the patients lung function was considered the forced expiratory volume in one second (FEV1) and the results were analyzed with SPSS. ResultsThere was an increase in the incidence of Chryseobacterium spp. with 17 isolates from 9 patients. Three patients had chronic colonization by this microorganism and one showed significant impairment of lung function. Seven patients showed also colonization with Staphylococcus aureus and 4 of them with Pseudomonas aeruginosa. ConclusionChryseobacterium spp. should be considered as a new emerging opportunistic pathogen in patients with CF. It is essential the clinical and microbiological monitoring of this group of patients for detection of Chryseobacterium spp. colonization and to prevent the chronic infection. In these circumstances it must assess its possible eradication, though its clinical impact is unknown. Cotrimoxazole being the best treatment option.

Effect of therapeutic arsenic exposure on pulmonary function

Arsenic-contaminated drinking water has been associated with respiratory diseases and lung function impairment. Oral arsenic trioxide (ATO) is a standard treatment for acute promyelocytic leukaemia. This study aimed to explore the effect of therapeutic exposure to arsenic on lung function. This was a case-control cross-sectional study on patients with haematological malignancies with or without exposure to ATO. Full lung function tests and serum Clara cell protein 16 (CC16) were measured. There were 57 cases (arsenic exposed) and 57 matched controls (arsenic non-exposed) recruited. Among cases, the median duration of ATO exposure was 519 (194-1259) days. The mean FEV(1)/FVC ratio, FEV(1) (% predicted), and RV/TLC (%), as well as % subjects with FEV(1)/FVC below lower limits of normal (LLN), were similar in the two groups with or without arsenic exposure. However the mean TLC (% predicted) and DLCO/VA were significantly higher in arsenic-exposed versus non-exposed group (p = 0.01 and p = 0.008 respectively). There were mildly reduced FEV(1)/FVC ratio and FEF(25-75) (% predicted), largely within normal limits, among high level arsenic exposure compared with non-exposure (p = 0.01 and p = 0.05 respectively). Serum CC16 was comparable among both arsenic exposed and non-exposed groups. Therapeutic use of oral ATO for a median of around 1.5 years was not associated with clinically significant lung function impairment.

Lung function in post-poliomyelitis syndrome: a cross-sectional study

OBJECTIVE: To compare lung function between patients with post-poliomyelitis syndrome and those with sequelae of paralytic poliomyelitis (without any signs or symptoms of post-poliomyelitis syndrome), as well as between patients with post-poliomyelitis syndrome and healthy controls. METHODS: Twenty-nine male participants were assigned to one of three groups: control; poliomyelitis (comprising patients who had had paralytic poliomyelitis but had not developed post-poliomyelitis syndrome); and post-poliomyelitis syndrome. Volunteers underwent lung function measurements (spirometry and respiratory muscle strength assessment). RESULTS: The results of the spirometric assessment revealed no significant differences among the groups except for an approximately 27% lower mean maximal voluntary ventilation in the post-poliomyelitis syndrome group when compared with the control group (p = 0.0127). Nevertheless, the maximal voluntary ventilation values for the post-poliomyelitis group were compared with those for the Brazilian population and were found to be normal. No significant differences were observed in respiratory muscle strength among the groups. CONCLUSIONS: With the exception of lower maximal voluntary ventilation, there was no significant lung function impairment in outpatients diagnosed with post-poliomyelitis syndrome when compared with healthy subjects and with patients with sequelae of poliomyelitis without post-poliomyelitis syndrome. This is an important clinical finding because it shows that patients with post-poliomyelitis syndrome can have preserved lung function.

Respiratory Symptoms, Exhaled Nitric Oxide, and Lung Function Among Workers in Tanzanian Coffee Factories

To compare chronic respiratory symptoms, fractional exhaled nitric oxide (FENO), and lung function between Robusta and Arabica coffee workers and a control group. Chronic respiratory symptoms were assessed by a questionnaire (n = 138 coffee workers and n = 120 controls). The FENO was measured by NIOX MINO device (Aerocrine AB, Solna, Sweden). Lung function was examined by a portable spirometer. Coffee workers had higher prevalence of chronic respiratory and asthma symptoms than controls. Robusta coffee workers were exposed to higher levels of endotoxin and had more asthma symptoms than Arabica coffee workers (38% vs. 18%). Coffee workers had reduced lung function associated with cumulative exposure to total dust and endotoxin. Work in coffee factories is associated with small but significant lung function impairment. These changes were not associated with the level of FENO.

Secondhand smoke exposure induces acutely airway acidification and oxidative stress

Previous studies have shown that secondhand smoke induces lung function impairment and increases proinflammatory cytokines. The aim of the present study was to evaluate the acute effects of secondhand smoke on airway acidification and airway oxidative stress in never-smokers. In a randomized controlled cross-over trial, 18 young healthy never-smokers were assessed at baseline and 0, 30, 60, 120, 180 and 240min after one-hour secondhand smoke exposure at bar/restaurant levels. Exhaled NO and CO measurements, exhaled breath condensate collection (for pH, H(2)O(2) and NO(2)(-)/NO(3)(-) measurements) and spirometry were performed at all time-points. Secondhand smoke exposure induced increases in serum cotinine and exhaled CO that persisted until 240min. Exhaled breath condensate pH decreased immediately after exposure (p<0.001) and returned to baseline by 180min, whereas H(2)O(2) increased at 120min and remained increased at 240min (p=0.001). No changes in exhaled NO and NO(2)/NO(3) were observed, while decreases in FEV(1) (p<0.001) and FEV(1)/FVC (p<0.001) were observed after exposure and returned to baseline by 180min. A 1-h exposure to secondhand smoke induced airway acidification and increased airway oxidative stress, accompanied by significant impairment of lung function. Despite the reversal in EBC pH and lung function, airway oxidative stress remained increased 4h after the exposure. Clinical trial registration number (EudraCT): 2009-013545-28.

Altered lung function relates to inflammation in an acute LPS mouse model

Preclinical in vivo models of lipopolysaccharide (LPS) -induced acute lung injury are commonly used to recapitulate pathophysiological features of chronic obstructive pulmonary disease and acute exacerbations. The LPS-induced lung inflammation is well described; however, whether the inflammatory response relates temporally to specific alterations in lung function has not been elucidated.We have investigated the effects of acute LPS inhalation in mice up to 96 h post LPS. Quantitation of inflammatory cells and inflammatory mediators in bronchoalveolar lavage fluid and non-invasive and invasive lung function measurements were performed at corresponding time points. The inhibitory effect of the glucocorticoid, budesonide, on LPS-induced lung inflammation and lung function was determined.LPS inhalation induced distinct histopathological changes, and infiltration of inflammatory cells to the lungs peaked at 48 h. At this time point, significantly increased inflammatory mediators and significantly altered lung capacity and mechanics parameters were observed. Budesonide given per os prevented the LPS-induced lung inflammation and lung dysfunction.These results demonstrate a temporal relationship between the peak of inflammatory cell influx and significant impairment of lung function, suggestive of a causative role of inflammation. These results allow better understanding of the functional consequences of lung inflammation in respiratory diseases.

Work-related respiratory symptoms and lung function among solderers in the electronics industry: a meta-analysis

Research on the respiratory effect of exposure to solder fumes in electronics workers has been conducted since the 1970s, but has yielded inconsistent results. The aim of this meta-analysis was to clarify the potential association. Effect sizes with corresponding 95% confidence intervals (CIs) for odds of respiratory symptoms related to soldering and spirometric parameters of solderers were extracted from seven studies and pooled to generate summary estimates and standardized mean differences in lung function measures between exposed persons and controls. Soldering was positively associated with wheeze after controlling for smoking (meta-odds ratio: 2.60, 95% CI: 1.46, 4.63) and with statistically significant reductions in forced expiratory volume in 1s (FEV1) (-0.88%, 95% CI: -1.51, -0.26), forced vital capacity (FVC) (-0.64%, 95% CI: -1.18, -0.10), and FEV1/FVC (-0.35%, 95% CI: -0.65, -0.05). However, lung function parameters of solderers were within normal ranges [pooled mean FEV1: 97.85 (as percent of predicted), 95% CI: 94.70, 100.95, pooled mean FVC: 94.92 (as percent of predicted), 95% CI: 81.21, 108.64, and pooled mean FEV1/FVC: 86.5 (as percent), 95% CI: 78.01, 94.98]. Soldering may be a risk factor for wheeze, but may not be associated with a clinically significant impairment of lung function among electronics workers.

Hemolytic Phospholipase C Inhibition Protects Lung Function during Pseudomonas aeruginosa Infection

The opportunistic pathogen Pseudomonas aeruginosa causes both acute and chronic lung infections and is particularly problematic in patients with cystic fibrosis and those undergoing mechanical ventilation. Decreased lung function contributes significantly to morbidity and mortality during P. aeruginosa infection, and damage inflicted by P. aeruginosa virulence factors contributes to lung function decline. We sought to describe direct contribution of a bacterial phospholipase C/sphingomyelinase, PlcHR, to alteration of host lung physiology and characterize a potential therapeutic for protection of lung function. We infected C57Bl/6 mice with P. aeruginosa wild-type or isogenic plcHR deletion strains and measured lung function using computer-controlled ventilators. For in vivo testing, miltefosine was delivered intraperitoneally 1 hour after infection. Infection and respiratory endpoints were at 24 hours after infection. P. aeruginosa wild-type infection caused significant lung function impairment, whereas the effects of a ΔplcHR strain infection were much less severe. Surfactometry analysis of bronchoalveolar lavage fluid indicated that PlcHR decreased pulmonary surfactant function. Miltefosine has structural similarity to the PC and sphingomyelin substrates of PlcHR, and we found that it inhibits the cleavage of these choline-containing lipids in vitro. Miltefosine administration after P. aeruginosa infection limited the negative effects of PlcHR activity on lung function. We have directly linked production of a single virulence factor in P. aeruginosa with effects on lung function, and demonstrated that the inhibitor miltefosine protects lung function from PlcHR-dependent surfactant dysfunction.