Impaired Diffusing Capacity Research Articles

Effect of pulmonary flow heterogeneity and impaired diffusing capacity on oxygen uptake

Severe impairment of oxygenation in critically ill patients is a major cause of morbidity and mortality, and can occur even with normal alveolar ventilation and cardiac output under conditions of decreased diffusing capacity or increased flow heterogeneity. A theoretical model of pulmonary oxygen uptake under resting conditions is used to simulate decreased diffusing capacity (DL) as well as increased heterogeneity (characterized by an increase in the coefficient of variation [CV] of pulmonary capillary blood flow), with the assumed normal value of CV based on observations of microvascular networks. Under resting conditions with nominal values of DL and CV, the model predicts an oxygen saturation (SO2) of 97% (PO2 = 94 mmHg). Simulating a 10‐fold reduction in DL leads to an SO2 of 85% (PO2 = 51 mmHg), whereas doubling the CV from its normal value leads to an SO2 of 95% (PO2 = 78 mmHg); both of these predictions suggest a high degree of reserve in the healthy resting lung. However, simulating these conditions simultaneously leads to a large reduction in SO2 to 71% (PO2 = 37 mmHg), exhausting the reserve capacity of the lung and demonstrating the detrimental synergistic effect of heterogeneity in the context of an attenuated diffusing capacity. These results imply that a combination of increased heterogeneity and decreased diffusing capacity can explain the severe impairment in pulmonary oxygen uptake and decreased saturations seen in critical illness.Support or Funding InformationSupported by NIH grant HL070657.

Year in review 2015: Interstitial lung disease, pulmonary vascular disease, pulmonary function, sleep and ventilation, cystic fibrosis and paediatric lung disease.

Keywords: interstitial lung disease; lung function; paediatric lung disease; pulmonary vascular disease; sleep

Hyperhomocysteinemia as a Predictive Biomarker for Impaired Diffusion Capacity of the Lung for Carbon Monoxide

SESSION TITLE: Pulmonary Physiology Posters SESSION TYPE: Original Investigation Poster PRESENTED ON: Wednesday, October 28, 2015 at 01:30 PM - 02:30 PM PURPOSE: Research has suggested that Hyperhomocysteinemia increased the risk of thrombus formation, by irritating the linings of the blood vessels. Although Hyperhomocysteinemia is considered as a cardiovascular predictive biomarker but none of the studies have examined its role as a pulmonary risk factor. The purpose of the study was to describe the association of Hyperhomocysteinemia with pulmonary diffusion capacity. METHODS: Four hundred study subjects were randomly selected in an outpatient clinic in Texas. Demographic, laboratory and clinical information including co-morbid conditions (OSA, hypertension, diabetes, cardiac diseases) and measurement of the diffusion capacity for carbon monoxide (DCLCo) were obtained for each patient. Standard descriptive and logistic regression techniques were employed with outcome variable as impaired lung diffusion (DCLCo less than 70%) and predictor variable hyperhomocysteinemia (homocysteine >12μmol/L). RESULTS: 160 patients (41%) with impaired lung diffusion for CO were mostly older (74% older than 65), females, nonsmoker, and obese (62%). Out of these, 14.2% have mild, 10.5 moderate and 17.7% have severely impaired lung diffusion. Unadjusted logistic regression reveals high homocystein levels are associated with impaired lung diffusion capacity (OR 2.54, P=0.01). Multivariate analysis after controlling for age, gender, ethnicity and comorbid conditions indicated that Hyperhomocysteinemia is significantly associated with lung diffusion capacity impairment (OR 2.50, P=0.03). In asthmatic patients, association of Hyperhomocysteinemia and lung diffusion was statistically significant (OR 2.30, P=0.02); in nonasthmatic, the Hyperhomocysteinemia and DCLCo correlation was not significant. (OR 1.21, P=0.71) CONCLUSIONS: Hyperhomocysteinemia is associated with impaired lung diffusion in adult patients and specifically for those who were asthmatic. CLINICAL IMPLICATIONS: Risk-identification in specific patient population will improve the quality of customized care and dissemination of relevant information about co-morbid conditions as an additional health risk to the patients, which will result in early prevention and improved patient's outcomes. DISCLOSURE: The following authors have nothing to disclose: Gul Nowshad, Mohamad Ayass No Product/Research Disclosure Information

Relationship between linear and nonlinear dynamics of heart rate and impairment of lung function in COPD patients.

BackgroundIn chronic obstructive pulmonary disease (COPD), functional and structural impairment of lung function can negatively impact heart rate variability (HRV); however, it is unknown if static lung volumes and lung diffusion capacity negatively impacts HRV responses. We investigated whether impairment of static lung volumes and lung diffusion capacity could be related to HRV indices in patients with moderate to severe COPD.MethodsSixteen sedentary males with COPD were enrolled in this study. Resting blood gases, static lung volumes, and lung diffusion capacity for carbon monoxide (DLCO) were measured. The RR interval (RRi) was registered in the supine, standing, and seated positions (10 minutes each) and during 4 minutes of a respiratory sinus arrhythmia maneuver (M-RSA). Delta changes (Δsupine-standing and Δsupine-M-RSA) of the standard deviation of normal RRi, low frequency (LF, normalized units [nu]) and high frequency (HF [nu]), SD1, SD2, alpha1, alpha2, and approximate entropy (ApEn) indices were calculated.ResultsHF, LF, SD1, SD2, and alpha1 deltas significantly correlated with forced expiratory volume in 1 second, DLCO, airway resistance, residual volume, inspiratory capacity/total lung capacity ratio, and residual volume/total lung capacity ratio. Significant and moderate associations were also observed between LF/HF ratio versus total gas volume (%), r=0.53; LF/HF ratio versus residual volume, %, r=0.52; and HF versus total gas volume (%), r=−0.53 (P<0.05). Linear regression analysis revealed that ΔRRi supine-M-RSA was independently related to DLCO (r=−0.77, r2=0.43, P<0.05).ConclusionResponses of HRV indices were more prominent during M-RSA in moderate to severe COPD. Moreover, greater lung function impairment was related to poorer heart rate dynamics. Finally, impaired lung diffusion capacity was related to an altered parasympathetic response in these patients.

Perinatal hypoxia increases susceptibility to high-altitude polycythemia and attendant pulmonary vascular dysfunction.

Perinatal exposures exert a profound influence on physiological function, including developmental processes vital for efficient pulmonary gas transfer throughout the lifespan. We extend the concept of developmental programming to chronic mountain sickness (CMS), a debilitating syndrome marked by polycythemia, ventilatory impairment, and pulmonary hypertension that affects ∼10% of male high-altitude residents. We hypothesized that adverse perinatal oxygenation caused abnormalities of ventilatory and/or pulmonary vascular function that increased susceptibility to CMS in adulthood. Subjects were 67 male high-altitude (3,600-4,100 m) residents aged 18-25 yr with excessive erythrocytosis (EE, Hb concentration ≥18.3 g/dl), a preclinical form of CMS, and 66 controls identified from a community-based survey (n = 981). EE subjects not only had higher Hb concentrations and erythrocyte counts, but also lower alveolar ventilation, impaired pulmonary diffusion capacity, higher systolic pulmonary artery pressure, lower pulmonary artery acceleration time, and more frequent right ventricular hypertrophy, than controls. Compared with controls, EE subjects were more often born to mothers experiencing hypertensive complications of pregnancy and hypoxia during the perinatal period, with each increasing the risk of developing EE (odds ratio = 5.25, P = 0.05 and odds ratio = 6.44, P = 0.04, respectively) after other factors known to influence EE status were taken into account. Adverse perinatal oxygenation is associated with increased susceptibility to EE accompanied by modest abnormalities of the pulmonary circulation that are independent of increased blood viscosity. The association between perinatal hypoxia and EE may be due to disrupted alveolarization and microvascular development, leading to impaired gas exchange and/or pulmonary hypertension.

Polymorphisms in PDE4D are Associated with a Risk of COPD in Non-Emphysematous Koreans

Despite extensive effort, only a few chronic obstructive pulmonary disease (COPD)-associated genes have been suggested, indicating that there must be additional risk-associated loci. Here we aimed to identify additional COPD-associated SNPs and to explore the potential relationship between COPD subgroups and the SNPs in the Korean population. We performed a genome-wide association study (GWAS) with 990 Korean individuals; 102 COPD cases and 544 controls for GWAS using Affymetrix SNP array 5.0, and 173 COPD cases and 171 controls for replication. After validating the candidate single nucleotide polymorphisms (SNP), we performed subgroup analysis by disease phenotype. Through GWAS, we identified a novel SNP in the phosphodiesterase-4D (PDE4D) gene [rs16878037 (C>T), p = 1.66 ◊ 10−6] that was significantly associated with COPD. This signal in PDE4D was successfully replicated in the independent set (p = 0.041). When we combined the discovery and replication data, the association signal became more significant (p = 5.69 ◊ 10−7). In the COPD subgroup analysis, the T allele of rs16878037 was significantly more frequent in COPD patients without severe diffusion capacity impairment (mild mixed and obstruction-dominant group) than in patients with severe impairment (severe mixed and emphysema-dominant groups). This result supports that PDE4D polymorphisms might be involved in the susceptibility to COPD especially in non-emphysematous individuals and that they could also affect the responsiveness of the PDE4 inhibitor treatment.

Midregional pro-adrenomedullin and copeptin: exercise kinetics and association with the cardiopulmonary exercise response in comparison to B-type natriuretic peptide

Midregional pro-adrenomedullin (MR-proADM) and C-terminal pro-vasopressin (copeptin) are novel biomarkers providing prognostic information in various settings. We aimed to (1) assess the kinetics of MR-proADM and copeptin during cardiopulmonary exercise testing (CPET); (2) assess the relationship of MR-proADM and copeptin measured at rest with peak oxygen consumption (peak VO2) and other key CPET parameters; (3) compare this relationship to that of B-type natriuretic peptide (BNP). In 162 patients undergoing symptom-limited CPET for evaluation of exercise intolerance, MR-proADM, copeptin, and BNP were measured at rest and peak exercise. There was a significant rise in copeptin and BNP (p < 0.001) but not in MR-proADM (p = 0.60) from rest to peak exercise. MR-proADM (r = -0.57; p < 0.001) and BNP (r = -0.49; p < 0.001) but not copeptin were significantly and inversely related to peak VO2. MR-proADM was inversely correlated to the percentage of predicted heart rate achieved and peak oxygen pulse and directly related to the peak ventilation/carbon dioxide production relationship, the physiological dead space-to-tidal volume ratio, and the alveolo-arterial oxygen gradient (p ≤ 0.01 for all), and these associations were at least as strong as for BNP. In contrast, copeptin was not significantly related to any of these parameters (p > 0.05 for all). In contrast to BNP and copeptin, MR-proADM is not immediately affected by a maximal exercise test. MR-proADM but not copeptin is at least as good an indicator of low peak VO2 and CPET parameters reflecting an impaired cardiac output reserve, ventilatory efficiency and diffusion capacity as BNP, and thereby a global cardiopulmonary stress marker.

Interstitial pneumonitis after acetylene welding: A case report

Acetylene is a colorless gas commonly used for welding. It acts mainly as a simple asphyxiant. In this paper, however, we present a patient who developed a severe interstitial pneumonitis after acetylene exposure during aluminum welding. A 44-year old man was welding with acetylene, argon and aluminum electrode sticks in a non-ventilated aluminum tank for 2 h. Four hours after welding dyspnea appeared and 22 h later he was admitted at the Emergency Department due to severe respiratory insufficiency with pO2 = 6.7 kPa. Chest X-ray showed diffuse interstitial infiltration. Pulmonary function and gas diffusion tests revealed a severe restriction (55% of predictive volume) and impaired diffusion capacity (47% of predicted capacity). Toxic interstitial pneumonitis was diagnosed and high-dose systemic corticosteroid methylprednisolone and inhalatory corticosteroid fluticasone therapy was started. Computed Tomography (CT) of the lungs showed a diffuse patchy ground-glass opacity with no signs of small airway disease associated with interstitial pneumonitis. Corticosteroid therapy was continued for the next 8 weeks gradually reducing the doses. The patient's follow-up did not show any deterioration of respiratory function. In conclusion, acetylene welding might result in severe toxic interstitial pneumonitis that improves after an early systemic and inhalatory corticosteroid therapy.

Adipokines NUCB2/nesfatin-1 and visfatin as novel inflammatory factors in chronic obstructive pulmonary disease.

COPD (chronic obstructive pulmonary disease) is a common lung disease characterized by airflow limitation and systemic inflammation. Recently, adipose tissue mediated inflammation has gathered increasing interest in the pathogenesis of the disease. In this study, we investigated the role of novel adipocytokines nesfatin-1 and visfatin in COPD by measuring if they are associated with the inflammatory activity, lung function, or symptoms. Plasma levels of NUCB2/nesfatin-1 and visfatin were measured together with IL-6, IL-8, TNF-α, and MMP-9, lung function, exhaled nitric oxide, and symptoms in 43 male patients with emphysematous COPD. The measurements were repeated in a subgroup of the patients after four weeks' treatment with inhaled fluticasone. Both visfatin and NUCB2/nesfatin-1 correlated positively with plasma levels of IL-6 (r = 0.341, P = 0.027 and rho = 0.401, P = 0.008, resp.) and TNF-α (r = 0.305, P = 0.052 and rho = 0.329, P = 0.033, resp.) and NUCB2/nesfatin-1 also with IL-8 (rho = 0.321, P = 0.036) in patients with COPD. Further, the plasma levels of visfatin correlated negatively with pulmonary diffusing capacity (r = −0.369, P = 0.016). Neither of the adipokines was affected by fluticasone treatment and they were not related to steroid-responsiveness. The present results introduce adipocytokines NUCB2/nesfatin-1 and visfatin as novel factors associated with systemic inflammation in COPD and suggest that visfatin may mediate impaired pulmonary diffusing capacity.

HIV Infection Is Associated With Diffusing Capacity Impairment in Women

Respiratory dysfunction is common with HIV infection, but few studies have directly assessed whether HIV remains an independent risk factor for pulmonary function abnormalities in the antiretroviral therapy era. Additionally, few studies have focused on pulmonary outcomes in HIV+ women. We tested associations between risk factors for respiratory dysfunction and pulmonary outcomes in 63 HIV+ and 36 HIV-uninfected women enrolled in the Women's Interagency HIV Study. Diffusing capacity (DL(CO)) was significantly lower in HIV+ women (65.5% predicted vs. 72.7% predicted, P = 0.01), and self-reported dyspnea in HIV+ participants was associated with both DL(CO) impairment and airflow obstruction. Providers should be aware that DL(CO) impairment is common in HIV infection, and that either DL(CO) impairment or airflow obstruction may cause respiratory symptoms in this population.

Clinical characteristics and lung function in chronic obstructive pulmonary disease complicated with impaired peripheral oxygenation

During exercise testing, patients with chronic obstructive pulmonary disease (COPD) often present with ventilatory limitations and various combinations of impaired peripheral oxygenation (IPO) to the exercising muscles. The entities of IPO include anemia, circulation impairment and deconditioning. COPD-IPO is not widely accepted as being a subgroup of COPD. Therefore, the aim of this study was to evaluate the clinical features of COPD-IPO patients. Forty-seven COPD patients underwent cardiopulmonary exercise testing. COPD-IPO was identified when all IPO variables had abnormal values. The patients who did not meet the COPD-IPO criteria were defined as the NIPO group. The variables with abnormal values included peak oxygen uptake (VO₂) <85% predicated, anaerobic threshold <40% VO₂max pred, VO₂-work rate slope <8.6 ml/watt, oxygen pulse <80%pred, and ventilatory equivalents for O₂ and CO₂ at nadir (>31 and >34, respectively). Anthropometrics, biochemistry, and lung function were compared between the groups. Forty-six COPD patients were enrolled after excluding one patient who had technical difficulties in performing the exercise tests. Despite FEV1 and FVC being similarly reduced (p = NS) between the groups, the COPD-IPO (n = 13, 28%) patients had lower body mass index and were taller, and had impaired diffusing capacity and larger total lung capacity and air-trapping (all p < 0.05). We concluded that COPD patients with all six variables having abnormal values are a unique subgroup and that identification of these patients is worthwhile for further investigations and management such as exercise training and nutritional supplements.

Midregional-pro-adrenomedullin but not copeptin represents a marker of overall ardiopulmonary stress

Background: Midregional pro-adrenomedullin (MR-pro ADM) and C-terminal pro-vasopressin (copeptin) provide prognostic information in a variety of settings. However, little is known about the relationship of these novel bio markers with the cardiopulmonary exercise testing (CPET) response. We sought to assess the relationship between MR-proADM and copeptin and peak oxygen consumption (peak VO2) and other key CPET parameters and to compare it to the established B-type natriuretic peptide (BNP). Methods: In 162 consecutive patients with a broad spectrum of pulmonary and cardiac function undergoing symptom-limited CPET for evaluation of exercise intolerance, MR-proADM, copeptin, and BNP plasma concentrations were measured immediately before CPET. Results: The median (interquartile range) MR-proADM, copeptin and BNP plasma concentration were 0.58 (0.44-0.77) nmol/l, 6.2 (4.5-10.3) pmol/l and 42 (17-103 ng/l) respectively. There were significant inverse correlations between peak VO2 and both MR-proADM and BNP but not copeptin (r= -0.57, p 0.05 for all). Conclusion: High MR-proADM but not copeptin is at least as good an indicator of low peak VO2 as BNP and is a marker of CPET parameters reflecting an impairment of the cardiac output reserve, ventilatory inefficiency, and impaired diffusion capacity, and thereby represents a marker of overall cardiopulmonary stress, which likely explains its strong prognostic value.

Comparison of different measures of diffusing capacity for carbon monoxide (DLCO) in systemic sclerosis

In systemic sclerosis (SSc), impaired diffusing capacity for carbon monoxide (DLCO) can indicate interstitial lung disease (ILD), pulmonary hypertension (PH), and/or other disease manifestations, including anemia. We undertook this study to compare the various measures of DLCO in the setting of a complex disease like SSc. We analyzed the pulmonary function tests of a cohort of SSc subjects, as a whole and among subjects with isolated PH and ILD separately. Associations were assessed using Spearman correlation coefficients, Student's t tests, and F tests by one-way ANOVA. P values <0.05 were considered statistically significant. This study included 225 subjects (mean age, 57 years; 88 % women; mean disease duration, 9.6 years; 32 % with diffuse disease, 44 % with ILD, and 17 % with PH). Mean percent predicted DLCO values were 75 % for DLCOsb and 83 % for DLCOrb. Adjustment for alveolar volume (VA) resulted in near normalization of both DLCOsb/VAsb (91 %) and DLCOrb/VArb (91 %). Subjects with ILD had significantly lower DLCOsb but not DLCOsb/VAsb, whereas those with PH had significantly lower DLCOsb and DLCOsb/VAsb. Among the various measures of DLCO, DLCOsb had the strongest and most consistent associations with clinical outcomes of interest. Adjusting for alveolar volume dampened the associations except with PH, with which DLCOsb/VAsb was more strongly associated than DLCOsb. Low DLCOsb is the most sensitive measure to detect abnormalities in gas exchange in SSc but reflects both parenchymal lung disease and pulmonary vascular disease. Low DLCOsb/VAsb is more specific for pulmonary vascular disease and should be the preferred measure of gas exchange in SSc.

THU0330 Pulmonary Function and Computed Tomography Imaging in Primary SjöGren’s Syndrome and Risk Factors for Lung Complication in a Large Cohort

BackgroundPulmonary involvement is common in primary Sjögren’s syndrome (pSS). Characteristics of pulmonary function and computed tomography imaging for pSS-associated lung disease which are feasible in clinic were less studied. In...

The impact of emphysema in pulmonary fibrosis

Several groups have described a syndrome in which idiopathic pulmonary fibrosis (IPF) coexists with pulmonary emphysema. This comes as no surprise since both diseases are associated with a history of exposure to cigarette smoke. The syndrome of combined pulmonary fibrosis and emphysema (CPFE) is characterised by upper lobe emphysema and lower lobe fibrosis. Physiological testing of these patients reveals preserved lung volume indices contrasted by markedly impaired diffusion capacity. The incidence of CPFE remains unknown but several case series suggest that this subgroup may comprise up to 35% of patients with IPF. CPFE is a strong determinant of associated pulmonary hypertension (PH). In addition, CPFE has major effects on measures of physiological function, exercise capacity and prognosis, and may affect the results of pulmonary fibrosis trials. Further studies are needed to ascertain the aetiology, morbidity, mortality and management of the CPFE syndrome, with or without PH, and to evaluate novel therapeutic options in CPFE.

HLA Distribution in COPD Patients

Background: Auto-immunity may contribute to the pathogenesis of chronic obstructive pulmonary disease (COPD), particularly to the presence of emphysema. Auto-immune diseases are characterized by an abnormal distribution of HLA class II alleles (DR and DQ). The distribution of DRB1 and DQB1 alleles has not been investigated in COPD. Methods: To this end, HLA medium-low resolution typing was performed following standardized protocols in 320 clinically stable COPD patients included in the PAC-COPD study. Results were compared with controls of the same geographical and ethnic origin, and potential relationships with the severity of airflow limitation and lung diffusing capacity impairment were explored in patients with COPD. Results: The distribution of DRB1 and DQB1 alleles in COPD was similar to that of controls except for a significantly higher prevalence of DRB1*14 in patients with severe airflow limitation and low diffusing capacity. Conclusions: By and large, HLA distribution was similar in COPD patients and controls, but the HLA class II allele DRB1*14 may contribute to the pathogenesis of severe COPD with emphysema.

Contributors to diffusion impairment in HIV-infected persons.

Abnormal diffusing capacity is common in HIV-infected individuals, including never smokers. Aetiologies for diffusing capacity impairment in HIV are not understood, particularly in those without a history of cigarette smoking. Our study was a cross-sectional analysis of 158 HIV-infected individuals without acute respiratory symptoms or infection with the aim to determine associations between a diffusing capacity of the lung for carbon monoxide (D(LCO)) % predicted and participant demographics, pulmonary spirometric measures (forced expiratory volume in 1 s (FEV1) and FEV1/forced vital capacity), radiographic emphysema (fraction of lung voxels < -950 Hounsfield units), pulmonary vascular/cardiovascular disease (echocardiographic tricuspid regurgitant jet velocity, N-terminal pro-brain natriuretic peptide) and airway inflammation (induced sputum cell counts), stratified by history of smoking. The mean D(LCO) was 65.9% predicted, and 55 (34.8%) participants had a significantly reduced D(LCO) (<60% predicted). Lower D(LCO) % predicted in ever-smokers was associated with lower post-bronchodilator FEV1 % predicted (p<0.001) and greater radiographic emphysema (p=0.001). In never-smokers, mean±SD D(LCO) was 72.7±13.4% predicted, and D(LCO) correlated with post-bronchodilator FEV1 (p=0.02), sputum neutrophils (p=0.03) and sputum lymphocytes (p=0.009), but not radiographic emphysema. Airway obstruction, emphysema and inflammation influence D(LCO) in HIV. Never-smokers may have a unique phenotype of diffusing capacity impairment. The interaction of multiple factors may account for the pervasive nature of diffusing capacity impairment in HIV infection.

Idiopathic Pulmonary Fibrosis—Clinical presentation, outcome and baseline prognostic factors in a Portuguese cohort

IntroductionIdiopathic Pulmonary Fibrosis (IPF) is the most common disease in the subgroup of idiopathic interstitial pneumonias. It is inevitably associated to a bad prognosis, although assuming a highly variable clinical course. MethodsPatients with IPF, observed at Interstitial Lung Diseases outpatient clinic of Centro Hospitalar de São João – Porto, Portugal, were identified and clinical, functional, radiological and bronchoalveolar lavage (BAL) parameters were reviewed. Their clinical course and survival were analyzed in order to identify prognostic factors. ResultsEighty-one patients were included, with a mean age at diagnosis of 63.8 years old. At diagnosis, the main functional abnormalities were restrictive physiology, reduced lung diffusion and exercise capacity impairment. Clinical course was mainly slowly progressive (72.3%). Ten patients (13.2%) had a rapid progression and 11 (14.5%) patients had an acute exacerbation during the course of the disease. IPF's rapid progression was associated to a higher functional impairment at diagnosis, namely in what is related with Functional Vital Capacity (FVC) and Total Lung Capacity (TLC). Median survival was 36 months. A significant difference in survival was observed among different types of clinical course – 41 months for slow progressors and 9 months for rapid progressors. Lower levels of FVC, TLC, six-minute walk test (6MWT) distance and rest PaO2, and higher BAL neutrophil count were associated with poorer survival in univariate analysis. ConclusionThe analysis of this group of IPF patients confirms two clearly different phenotypes, slow and rapid progressors. Those phenotypes seem to have different presentations and a remarkably different natural history. These results could mean different physiopathologic pathways, which could implicate different therapeutic approaches.

Lung function outcome at school age in very low birth weight children

The aim of this study was to assess pulmonary function and its predictors in very low birth weight (birth weight ≤1,500 g) children (VLBWc) with or without bronchopulmonary dysplasia (BPD), born at gestational age ≤32 weeks at a single tertiary center during 1996-1999, after the introduction of surfactant therapy. Of the 120 surviving VLBW children, 48 (40%) VLBWc (22 with prior-BPD) at age 8.5 ± 1.0 years and 46 age-matched controls (8.8 ± 1.4 years) born at term, underwent lung function study. Adjusted values (z-score) of forced vital capacity (z-FVC), forced expiratory volume in 1 sec (z-FEV1), forced expiratory flow 25-75% (z-FEF25-75), carbon monoxide lung diffusion capacity (z-DLCO), and DLCO/alveolar volume (z-DLCO/VA) were significantly lower than controls (mean difference, 95% CI: -1.35, -1.81 to -0.90, P < 0.001; -1.31, -1.73 to -0.90, P < 0.001; -0.87, -1.29 to -0.46, P < 0.001; -0.98, -1.72 to -0.23, P < 0.001; -0.70, -1.22 to -0.18, P < 0.05; respectively). Residual volume (z-RV) and RV/total lung capacity (RV/TLC) ratio (%) were significantly higher in VLBWc than controls (mean difference, 95% CI: 1.06, 0.44 to 1.68, P < 0.001; 9.54%, 5.73 to 13.3%, P < 0.001; respectively). No differences were found in lung function between VLBWc (no-BPD vs. BPD) with the exception of a significant higher RV/TLC ratio in the BPD-subgroup (mean difference, 95% CI: 7.0%, 0.4 to 13%, P = 0.03). Lung function abnormalities were found in 30 (63%) VLBWc with evidence of airway obstruction and diffusing capacity impairment. A weak relationship was observed between gestational age with z-FVC (r = 0.30, P = 0.04), birth weight with z-FEV1 (r = 0.30, P = 0.04) and RV/TLC ratio (r = -0.49, P = 0.001). The duration of oxygen treatment correlated negatively with the z-DLCO/Va (r = -0.5, P = 0.02). No differences were found in FeNO levels between VLBWc and controls. VLBWc at school age showed lung function abnormalities characterized by airway obstruction, hyperinflation, and diffusion impairment. Neonatal lung damage together with preterm birth may play a role in worsening the functional respiratory outcome.

45-jähriger Patient mit progredienter Dyspnoe und „crazy paving“

A 45-year-old man referred with progressive shortness of breath. Chest X-ray revealed a diffuse parenchymal process in the lungs, which was characterized as a "crazy paving" pattern in the thoracic CT. Pulmonary function test showed severe impairment of diffusion capacity and apparent respiratory insufficiency. Bronchoalveolar lavage and histological examinations of transbronchial lung biopsies revealed alveolar proteinosis. Because of the presence of anti-granulocyte macrophage colony-stimulating factor (GM-CSF) autoantibodies, a primary form of this disorder was diagnosed. Therapeutic whole-lung lavage was performed twice and resulted in a continuing remission.