Assessing the applicability of the new Global Lung Function Initiative reference values for the diffusing capacity of the lung for carbon monoxide in a large population set.

BACKGROUND: The single-breath diffusing capacity of the lung for carbon monoxide (DLCO) interpretation needs the comparison of measured values to reference values. In 2017, the Global Lung Function Initiative published new reference values (GLI-2017) for DLCO, alveolar volume (VA) and transfer coefficient of the lung for carbon monoxide (KCO). We aimed to assess the applicability of GLI-2017 reference values for DLCO on a large population by comparing them to the European Community of Steel and Coal equations of 1993 (ECSC-93) widely used. METHODS: In this retrospective study, spirometric indices, total lung capacity, DLCO, VA and KCO were measured in adults classified in 5 groups (controls, asthma, chronic bronchitis, cystic fibrosis, and interstitial lung diseases (ILD)). Statistical analysis comparing the 2 equations sets were stratified by sex. RESULTS: 4180 tests were included. GLI-2017 z-scores of the 3 DLCO indices of the controls (n = 150) are nearer to 0 (expected value in a normal population) than ECSC-93 z-scores. All groups combined, in both genders, DLCO GLI-2017 z-scores and %predicted are significantly higher than ECSC z-scores and %predicted. In the ILD group, differences between the 2 equation sets depend on the DLCO impairment severity: GLI-2017 z-scores are higher than ECSC z-scores in patients with no or "mild" decrease in DLCO, but are lower in "moderate" or "severe" decrease. CONCLUSION: GLI-2017 reference values for DLCO are more suitable to our population and influence the diagnostic criteria and severity definition of several lung diseases.

Addressing Reduced Laboratory-Based Pulmonary Function Testing During a Pandemic.

To reduce the spread of the severe acute respiratory syndrome coronavirus 2, many pulmonary function testing (PFT) laboratories have been closed or have significantly reduced their testing capacity. Because these mitigation strategies may be necessary for the next 6 to 18 months to prevent recurrent peaks in disease prevalence, fewer objective measurements of lung function will alter the diagnosis and care of patients with chronic respiratory diseases. PFT, which includes spirometry, lung volume, and diffusion capacity measurement, is essential to the diagnosis and management of patients with asthma, COPD, and other chronic lung conditions. Both traditional and innovative alternatives to conventional testing must now be explored. These may include peak expiratory flow devices, electronic portable spirometers, portable exhaled nitric oxide measurement, airwave oscillometry devices, and novel digital health tools such as smartphone microphone spirometers and mobile health technologies along with integration of machine learning approaches. The adoption of some novel approaches may not merely replace but could improve existing management strategies and alter common diagnostic paradigms. With these options comes important technical, privacy, ethical, financial, and medicolegal barriers that must be addressed. However, the coronavirus disease 19 pandemic also presents a unique opportunity to augment conventional testing by including innovative and emerging approaches to measuring lung function remotely in patients with respiratory disease. The benefits of such an approach have the potential to enhance respiratory care and empower patient self-management well beyond the current global pandemic.

Unexpected radiation pneumonitis after SIRT with significant decrease in DLCO with internal radiation exposure: a case report.

BACKGROUND: In the last years, Selective Internal Radiation Therapy (SIRT), using biocompatible Yttrium-90 (90Y) labeled microspheres have emerged for the treatment of malignant hepatic tumors. Unfortunately, a significant part of 90Y-labeled microspheres may shunt to the lungs after intraarterial injection. It can be predictable by infusing technetium-99 m-labeled macro-aggregated albumin particles through a catheter placed in the proper hepatic artery depending on the lobe to be treated with performing a quantitative lung scintigraphy. Radiation pneumonitis (RP) can occur 1 to 6 months after the therapy, which is a rare but severe complication of SIRT. Prompt timing of steroid treatment is important due to its high mortality rate. On the other hand, pulmonary diffusion capacity measured by carbon monoxide (DLCO) is an excellent way to measure the diffusing capacity because carbon monoxide is present in minimal amount in venous blood and binds to hemoglobin in the same manner as oxygen. Some authors reported that the most consistent changes after radiation therapy (RT) are recorded with this quantitative reproducible test. The relationship between the proportional reductions in DLCO and the severity of RP developing after this therapy may prove to be clinically significant. CASE PRESENTATION: We herein present a patient who developed RP after SIRT that could be quantified using DLCO. To the best of our knowledge, this case is the first who developed unexpected RP after SIRT with significant decrease in DLCO with internal radiation exposure. CONCLUSIONS: RP is a very rare complication and may lead to a fatal outcome. Decline in DLCO could be a valuable parameter for follow-up and to identify potential candidates for RP and could be also another trigger for administration of steroid therapy with prompt timing in this patient group.

Impact of diffusing lung capacity before and after neoadjuvant concurrent chemoradiation on postoperative pulmonary complications among patients with stage IIIA/N2 non-small-cell lung cancer.

BACKGROUND AND OBJECTIVE: This study aims to evaluate the impact of diffusing capacity of the lung for carbon monoxide (DLco) before and after neoadjuvant concurrent chemoradiotherapy (CCRT) on postoperative pulmonary complication (PPC) among stage IIIA/N2 non-small-cell lung cancer (NSCLC) patients. METHODS: We retrospectively studied 324 patients with stage IIIA/N2 NSCLC between 2009 and 2016. Patients were classified into 4 groups according to DLco before and after neoadjuvant CCRT; normal-to-normal (NN), normal-to-low (NL), low-to-low (LL), and low-to-very low (LVL). Low DLco and very low DLco were defined as DLco < 80% predicted and DLco < 60% predicted, respectively. RESULTS: On average, DLco was decreased by 12.3% (±10.5) after CCRT. In multivariable-adjusted analyses, the incidence rate ratio (IRR) for any PPC comparing patients with low DLco to those with normal DLco before CCRT was 2.14 (95% confidence interval (CI) = 1.36-3.36). Moreover, the IRR for any PPC was 3.78 (95% CI = 1.68-8.49) in LVL group compared to NN group. The significant change of DLco after neoadjuvant CCRT had an additional impact on PPC, particularly after bilobectomy or pneumonectomy with low baseline DLco. CONCLUSIONS: The DLco before CCRT was significantly associated with risk of PPC, and repeated test of DLco after CCRT would be helpful for risk assessment, particularly in patients with low DLco before neoadjuvant CCRT.

Frailty and geriatric conditions in older patients with idiopathic pulmonary fibrosis.

BACKGROUND: Functional status, an important predictor of health outcomes in older patients, has not been studied in an IPF population. This study aimed to determine the prevalence of frailty and geriatric conditions in older patients with IPF. METHODS: IPF patients age ≥65 years were identified prospectively at the University of Michigan. Frailty was assessed using the Fried frailty phenotype. Questionnaires addressing functional status, geriatric conditions and symptoms were administered. Quantitative measurement of pectoralis muscle area was performed. Patient variables were compared among different frailty groups. RESULTS: Of the 50 participants, 48% were found to be frail and 40% had ≥2 geriatric conditions. Frailty was associated with increased age, lower lung function, shorter 6-min walk distance, higher symptom scores and a greater number of comorbidities, geriatric conditions and functional limitations (p < 0.05). Pectoralis muscle area was nearly significant (p = 0.08). Self-reported fatigue score (odds ratio [OR] = 2.13, confidence interval [CI] 95% 1.23-3.70, p = 0.0068) and diffusion capacity (OR = 0.54 CI 95% 0.35-0.85, p = 0.0071) were independent predictors of frailty. CONCLUSIONS: Frailty and geriatric conditions are common in older patients with IPF. The presence of frailty was associated with objective (diffusion capacity) and subjective (self-reported fatigue score) data. Longitudinal evaluation is necessary to determine impact of frailty on disease-related outcomes in IPF.

Independent Prognostic Value of Pulmonary Diffusing Capacity in Nonsmoking Patients with Chronic Heart Failure.

The diffusing capacity of the lung for carbon monoxide (DLCO) is indicative of the alveolar-capillary membrane function. A reduced DLCO is associated with poor prognosis in chronic heart failure (HF). However, the significance of DLCO as an independent prognostic predictor has not been established. Here, we aimed to determine the prognostic value of DLCO in patients with chronic HF.We enrolled 214 patients (139 females, mean age: 63 ± 16 years, left ventricular ejection fraction [LVEF]: 45 ± 21%) with stable chronic HF who underwent pulmonary function tests. Only never smokers were included in the analysis because smoking can decrease DLCO.During a median follow-up period of 2.1 years, 52 patients (24.3%) experienced cardiac events, including unplanned HF admissions, left ventricular assist device (LVAD) implantations, all-cause deaths, and cardiopulmonary arrests (CPAs). The median percent predicted DLCO (%DLCO) was 87.3%. In a Cox regression analysis, a %DLCO of ≤87.3% was independently associated with the cardiac events, even after adjusting for age, sex, systolic blood pressure (SBP), LVEF, anemia, brain natriuretic peptide, estimated glomerular filtration rate (eGFR), and prior HF admission (hazard ratio [HR]: 1.87, 95% confidence interval: 1.03-3.53, P = 0.030).A reduced DLCO is an independent predictor of poor prognosis in nonsmoking patients with chronic HF.

Hyperpolarised xenon magnetic resonance spectroscopy for the longitudinal assessment of changes in gas diffusion in IPF.

Prognosticating idiopathic pulmonary fibrosis (IPF) is challenging, in part due to a lack of sensitive biomarkers. A recent article in Thorax described how hyperpolarised xenon magnetic resonance spectroscopy may quantify regional gas exchange in IPF lungs. In a population of patients with IPF, we find that the xenon signal from red blood cells diminishes relative to the tissue/plasma signal over a 12-month time period, even when the diffusion factor for carbon monoxide is static over the same time period. We conclude that hyperpolarised 129Xe MR spectroscopy may be sensitive to short-term changes in interstitial gas diffusion in IPF.

Acute effects of hypertonic saline inhalation on nitric oxide pulmonary diffusing capacity in healthy adults.

We investigated acute effects of inhalation of hypertonic saline solution (HSS) and oxygen (O2, control exposure) on pulmonary diffusing capacity for nitric oxide (DLNO) and carbon monoxide (DLCO). In a randomized crossover study, 20 healthy, non-smoking subjects were allocated to short-term inhalation of HSS or O2. Spirometry [(forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC)] and combined single-breath DLNO-DLCO measurements were performed before and immediately after inhalation of either HSS or O2. Percent changes were presented as median values (interquartile range). After HSS inhalation, DLNO, FEV1 and FVC were decreased by -3.0% (-7.3, 0.5), -3.1% (-4.2, -1.6) and -1.2% (-3.3, 0.6), respectively (all P < 0.05), without significant effect on DLCO. No changes in spirometry and diffusing capacity were observed following O2 inhalation. Acute inhalation of HSS causes a slight decrease in membrane conductance, probably as a result of fluid imbalance at the alveolar surface and interstitial fluid accumulation, both of which could impair gas exchange.

Acute effects of combined exercise and oscillatory positive expiratory pressure therapy on sputum properties and lung diffusing capacity in cystic fibrosis: a randomized, controlled, crossover trial.

BACKGROUND: Regular airway clearance by chest physiotherapy and/or exercise is critical to lung health in cystic fibrosis (CF). Combination of cycling exercise and chest physiotherapy using the Flutter® device on sputum properties has not yet been investigated. METHODS: This prospective, randomized crossover study compared a single bout of continuous cycling exercise at moderate intensity (experiment A, control condition) vs a combination of interval cycling exercise plus Flutter® (experiment B). Sputum properties (viscoelasticity, yield stress, solids content, spinnability, and ease of sputum expectoration), pulmonary diffusing capacity for nitric oxide (DLNO) and carbon monoxide (DLCO) were assessed at rest, directly and 45 min post-exercise (recovery) at 2 consecutive visits. Primary outcome was change in sputum viscoelasticity (G', storage modulus; G", loss modulus) over a broad frequency range (0.1-100 rad.s- 1). RESULTS: 15 adults with CF (FEV1range 24-94% predicted) completed all experiments. No consistent differences between experiments were observed for G' and G" and other sputum properties, except for ease of sputum expectoration during recovery favoring experiment A. DLNO, DLCO, alveolar volume (VA) and pulmonary capillary blood volume (Vcap) increased during experiment A, while DLCO and Vcap increased during experiment B (all P < 0.05). We found no differences in absolute changes in pulmonary diffusing capacity and its components between experiments, except a higher VA immediately post-exercise favoring experiment A (P = 0.032). CONCLUSIONS: The additional use of the Flutter® to moderate intensity interval cycling exercise has no measurable effect on the viscoelastic properties of sputum compared to moderate intensity continuous cycling alone. Elevations in diffusing capacity represent an acute exercise-induced effect not sustained post-exercise. TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT02750722 ; URL: clinical.trials.gov; Registration date: April 25th, 2016.

Decreased Lung Function and All-Cause Mortality in HIV-infected Individuals.

RATIONALE: Human immunodeficiency virus (HIV) infection is associated with pulmonary disease and worse lung function, but the relationship of lung function with survival in HIV is unknown. OBJECTIVES: To determine whether lung function is associated with all-cause mortality in HIV-infected individuals. METHODS: HIV-infected participants from cohorts in three locations underwent pre- and post-bronchodilator spirometry and determination of single-breath diffusing capacity of the lung for carbon monoxide (DlCO) in 2008-2009, computed tomographic (CT) scanning of the chest for quantitative emphysema and airway measures, and echocardiography for estimated left ventricular systolic and diastolic function and tricuspid regurgitant velocity. Bivariate analysis and multivariable Cox proportional hazards models were used to determine whether decreased lung function was independently associated with increased all-cause mortality. Models were adjusted for covariates including age, sex, body mass index, smoking status, self-reported hepatitis C status, HIV viral levels, CD4+ T-cell counts, hemoglobin, antiretroviral therapy, and illicit drug use. RESULTS: Overall, 396 HIV-infected participants underwent pulmonary function testing. Thirty-two participants (8%) died during a median follow-up period of 69 months. A post-bronchodilator FEV1-to-FVC ratio less than 0.7 (hazard ratio [HR], 2.47; 95% confidence interval [CI], 1.10-5.58) and a DlCO less than 60% (HR, 2.28; 95% CI, 1.08-4.82) were independently associated with worse mortality. Also, hepatitis C (HR, 2.68; 95% CI, 1.22-5.89) and baseline plasma HIV RNA level (HR per ln RNA copies/ml, 1.50; 95% CI, 1.22-1.86) were associated with mortality in HIV-infected participants. The only CT or echocardiographic measure associated with greater mortality in univariate analysis was greater wall thickness of medium-sized airways (HR for wall area percent, 1.08; 95% CI, 1.00-1.18; P = 0.051), but none of the CT or echocardiogram measures were associated with mortality in multivariable analysis. CONCLUSIONS: Airflow obstruction and impaired diffusing capacity appear to be associated with all-cause mortality in HIV-infected persons over an average of 6 years of follow-up. These data highlight the importance of lung dysfunction in HIV-infected persons and should be confirmed in larger cohorts and with extended follow-up periods. Clinical trial registered with www.clinicaltrials.gov (NCT00869544, NCT01326572).

Intra-session and inter-session variability of nitric oxide pulmonary diffusing capacity in adults with cystic fibrosis.

We evaluated the intra-session and inter-session variability of the diffusing capacity of nitric oxide (DLNO), carbon monoxide (DLCO), alveolar-capillary membrane diffusing capacity for carbon monoxide (DMCO) and pulmonary capillary blood volume (Vc) in patients with cystic fibrosis (CF). Patients performed single-breath diffusing capacity measurements during all of 3 consecutive study visits. Precision of gas diffusing parameters was quantified by within-subject standard deviation (SDws) and coefficient of variation (CV). Intra-session and inter-session reproducibility was determined by SDws*2.77. 15 clinically stable patients were included. The intra-session precision of gas diffusing parameters improved over the study visits. The inter-session SDws for DLNO, DLCO, DMCO, and Vc was 4.8, 1.3, 2.4, and 4.3, respectively. Reproducibility was 13.3, 3.8, 6.7 and 12.0mLmin-1mmHg-1; CV was 4.4, 4.7, 4.4 and 5.8%, respectively. The intra-session variability of DLNO, DLCO, DMCO and Vc improves with breath-hold maneuver training in test-naïve patients with CF, indicating a learning effect. Inter-session reproducibility data are lower than those previously reported in healthy subjects.

Chest wall resection for non-small cell lung cancer: A case-matched study of postoperative pulmonary function and quality of life.

BACKGROUND: To assess the pulmonary function and quality of life (QOL) after chest wall resection for non-small cell lung cancer. MATERIAL AND METHODS: One hundred and thirty-five patients (cases) who underwent pulmonary resection with chest wall removal were identified from January 1997 to December 2015. Propensity score matching (1:3) was applied to balance known confounders for pulmonary function and QOL between the cases and the control group who underwent pulmonary resection without chest wall invasion. Matched analyses were performed to compare perioperative mortality and morbidity, postoperative pulmonary function, overall QOL, and specific symptoms. RESULTS: Perioperative mortality and morbidity did not differ significantly between cases and controls, but the hospital stay was longer in cases than in controls (mean, 12.8 vs 8.9days; p<0.001), The decline of postoperative pulmonary forced vital capacity (FVC) and the percentage of predicted FVC (FVC%) was more obvious in cases than in controls at 6 months and 2 years after surgery, but there was no obvious decline in the forced expiratory volume in one second (FEV1), the percentage of predicted FEV1 (FEV1%), the diffusion capacity of the lung for carbon monoxide (DLCO) and the percentage of predicted DLCO (DLCO%) in cases compared with controls. No significant difference was observed between the two groups in scores for overall QOL, pain, fatigue, cough, dyspnea, appetite, hemoptysis, lung cancer symptoms, and normal activities. CONCLUSIONS: When chest wall resection is inevitable, it does not worse the QOL and pulmonary function of patients who underwent pulmonary resection with chest wall removal obviously compared with patients underwent pulmonary resection without chest wall invasion.

The history of the pulmonary diffusing capacity for nitric oxide DL,NO.

The DL,NO (TL,NO) had its unexpected origins in the Paris "events" of 1968 and the unsuccessful efforts of the UK tobacco industry in the 1970's to create a "safer cigarette". Adoption of the technique has been slow due to the instability of NO in air, lack of standardisation of the technique and lack of agreement as to whether DL,NO is equal to or merely reflects membrane diffusing capacity (DM). With the availability of inexpensive analysers, standardisation of the technique and publication of reference equations we believe that its worldwide use will increase.

Lung function abnormalities among service members returning from Iraq or Afghanistan with respiratory complaints.

BACKGROUND: Service members deploying to Afghanistan (OEF) and Iraq (OIF) often return with respiratory symptoms. We sought to determine prevalence of lung function abnormalities following OEF/OIF. METHODS: We identified OEF/OIF patients who had unexplained respiratory symptoms evaluated using lung function testing. Lung function data were summarized and analyzed for associations with demographic and deployment characteristics. RESULTS: We found 267 patients with unexplained cough or dyspnea, lung function testing and a history of OEF/OIF deployment. All patients had basic spirometry performed and 82 had diffusion capacity for carbon dioxide (DLCO) measured. The median (IQR) number of deployments and total days deployed were 1 (1-2) and 352.0 (209-583), respectively. There were 83 (36.6%) patients with abnormal spirometry, 53 (63.9%) of whom had an abnormal FEV1/FVC. Only one (1.2%) patient had an abnormal DLCO adjusted for alveolar volume. Of 104 patients who had post bronchodilator (BD) testing performed, six (5.8%) had a positive response by ATS criteria. We found no relationships between lung function and time in theater, deployment location, deployment frequency, or land based-deployment. Dyspnea and enlisted rank were associated with tobacco use and lower FEV1, and cough was associated with total number of deployments. CONCLUSIONS: Service members with respiratory complaints following OEF/OIF have a high prevalence of abnormalities on spirometry. Tobacco use, enlisted rank and total number of deployments were associated with symptoms or spirometric abnormalities.

Identification of five clusters of comorbidities in a longitudinal Japanese chronic obstructive pulmonary disease cohort.

BACKGROUND AND OBJECTIVES: Patients with chronic obstructive pulmonary disease (COPD) frequently suffer from various comorbidities. Recently, cluster analysis has been proposed to examine the phenotypic heterogeneity in COPD. In order to comprehensively understand the comorbidities of COPD in Japan, we conducted multicenter, longitudinal cohort study, called the Keio COPD Comorbidity Research (K-CCR). In this cohort, comorbid diagnoses were established by both objective examination and review of clinical records, in addition to self-report. We aimed to investigate the clustering of nineteen clinically relevant comorbidities and the meaningful outcomes of the clusters over a two-year follow-up period. MATERIAL AND METHODS: The present study analyzed data from COPD patients whose data of comorbidities were completed (n = 311). Cluster analysis was performed using Ward's minimum-variance method. RESULTS: Five comorbidity clusters were identified: less comorbidity; malignancy; metabolic and cardiovascular; gastroesophageal reflux disease (GERD) and psychological; and underweight and anemic. FEV1 did not differ among the clusters. GERD and psychological cluster had worse COPD assessment test (CAT) and Saint George's respiratory questionnaire (SGRQ) at baseline compared to the other clusters (CAT: p = 0.0003 and SGRQ: p = 0.00046). The rate of change in these scores did not differ within 2 years. The underweight and anemic cluster included subjects with lower baseline ratio of predicted diffusing capacity (DLco/VA) compared to the malignancy cluster (p = 0.036). CONCLUSIONS: Five clusters of comorbidities were identified in Japanese COPD patients. The clinical characteristics and health-related quality of life were different among these clusters during a follow-up of two years.

Cem anos do teste de difusão ao monóxido de carbono nas doenças pulmonares / One hundred years of carbon monoxide diffusion test in lung disease

Em 2015 fazem exatamente cem anos desde a primeira publicação a descrever um método de aferição da respiração única de permeabilidade dos gases. Atualmente, os testes são realizados por sistemas automatizados utilizando a manobra de respiração única já padronizada internacionalmente. Este artigo aborda as técnicas usadas nesta medida, as equações de normalidade existentes e como interpretar dos dados obtidos. A interpretação dos resultados obtidos devem ser feita de forma cuidadosa. Tanto doenças obstrutivas como restritivas podem causar redução da capacidade de difusão ao monóxido de carbono. Quando usado em indicações clínicas bem estabelecidas e, principalmente, quando os resultados são analisados em conjunto com a clínica, radiologia e a medida dos volumes e fluxos pulmonares, o teste da difusão pode ser uma rica ferramenta no auxílio diagnóstico e prognóstico. Os aparelhos atualmente disponíveis no mercado para realização do teste são extremamente confiáveis, provendo exames reprodutíveis e acurados, no entanto, são equipamentos caros, devendo ser importados o que dificulta a disseminação da técnica.

In 2015 make exactly one hundred years since the first report describing a single-breath method of measuring permeability of gases. Currently, tests are performed by automated systems using the single breath maneuver already internationally standardized. This article discusses the techniques used in this measure, the existing normal equations and how to interpret the data obtained. The interpretation of the results obtained should be done carefully. Both obstructive and restrictive diseases can cause reduced diffusion capacity for carbon monoxide. When used in well-established clinical indications and especially when the results are analyzed together with the clinical, radiology and the measured lung volumes and flows, the diffusion test can be a rich tool in the diagnosis and can also provide the prognosis. Devices currently available in the market for the test are extremely reliable, providing reproducible and accurate tests. However, they are expensive equipment and must be imported which hinders the spread of technology.

Computed tomography score and pulmonary function in infants with chronic lung disease of infancy.

Chronic lung disease of infancy (CLDI) remains a common outcome among infants born extremely prematurely. In older children and adults with lung disease, pulmonary function and computed tomography (CT) scores are used to follow up respiratory disease and assess disease severity. For infants and toddlers, however, these outcomes have been used very infrequently and most often, a dichotomous respiratory outcome (presence or absence of CLDI) is employed. We evaluated the performance of CT score and pulmonary function to differentiate infants and toddlers with CLDI from a control group. CT scans, forced expiratory flows and pulmonary diffusing capacity were obtained in 39 CLDI patients and 41 controls (aged 4-33 months). CT scans were quantified using a scoring system, while pulmonary function was expressed as Z-scores. CT score outperformed pulmonary function in identifying those with CLDI. There were no significant correlations between CT score and pulmonary function. CT score had a better performance than pulmonary function in differentiating individuals with CLDI; however, these outcomes may reflect differing components of the pulmonary pathophysiology of CLDI. This new information on pulmonary outcomes can assist in designing studies with these parameters. Future studies will be required to evaluate which of the outcomes can better detect improvement with therapeutic intervention and/or lung growth.

Nitric oxide diffusing capacity versus spirometry in the early diagnosis of emphysema in smokers.

The diffusion capacity for nitric oxide (DLNO) is independent of pulmonary capillary blood volume and equals the membrane diffusing capacity. Therefore the DLNO could be more sensitive in detecting alveolar destruction than the DLCO. We measured flow-volumes curves, DLNO, DLCO, the transfer coefficients KNO (DLNO/VA) and KCO (DLCO/VA) and performed computed tomography (CT) scans in 263 randomly selected heavy smokers. Subjects with areas > or =1% of the total lung volume showing an attenuation <-950 Hounsfield Units were considered to have emphysema. In 36 subjects emphysema was diagnosed with CT, a low KNO was present in 94 subjects, and in 95 subjects a FEV1/FVC ratio <70% was seen. The area under the ROC curve for detection CT-based emphysema was 0.894 for the KNO, 0.822 for the KCO and 0.795 for FEV1/FVC, meaning that the KNO has a slightly higher sensitivity to detect emphysema than the KCO and FEV1/FVC. The positive predictive value of KNO however was low (34.7%), while the negative predictive value of KNO was very high (98.2%), indicating an emphysema exclusion test. The DLNO/DLCO ratio is significantly higher in the study group compared to normal subjects.

Membrane diffusion- and capillary blood volume measurements are not useful as screening tools for pulmonary arterial hypertension in systemic sclerosis: a case control study.

BACKGROUND: There is no optimal screening tool for the assessment of pulmonary arterial hypertension (PAH) in patients with systemic sclerosis (SSc). A decreasing transfer factor of the lung for CO (TLCO) is associated with the development of PAH in SSc. TLCO can be partitioned into the diffusion of the alveolar capillary membrane (Dm) and the capillary blood volume (Vc). The use of the partitioned diffusion to detect PAH in SSc is not well established yet. This study evaluates whether Dm and Vc could be candidates for further study of the use for screening for PAH in SSc. METHODS: Eleven SSc patients with PAH (SScPAH+), 13 SSc patients without PAH (SScPAH-) and 10 healthy control subjects were included. Pulmonary function testing took place at diagnosis of PAH. TLCO was partitioned according to Roughton and Forster. As pulmonary fibrosis in SSc influences values of the (partitioned) TLCO, these were adjusted for fibrosis score as assessed on HRCT. RESULTS: TLCO as percentage of predicted (%) was lower in SScPAH+ than in SScPAH- (41 +/- 7% vs. 63 +/- 12%, p < 0.0001, respectively). Dm% in SScPAH+ was decreased as compared with SScPAH- (22 +/- 6% vs. 39 +/- 12%, p < 0.0001, respectively), also after adjustment for total fibrosis score (before adjustment: B = 17.5, 95% CI 9.0-25.9, p = < 0.0001; after adjustment: B = 14.3, 95% CI 6.0-21.7, p = 0.008). No difference was found in Vc%. There were no correlations between pulmonary hemodynamic parameters and Dm% in the PAH groups. CONCLUSION: SScPAH+ patients have lower Dm% than SScPAH- patients. There are no correlations between Dm% and hemodynamic parameters of PAH in SScPAH+. These findings do not support further study of the role of partitioning TLCO in the diagnostic work- up for PAH in SSc.

Heterogeneity in combined pulmonary fibrosis and emphysema.

BACKGROUND: Combined pulmonary fibrosis and emphysema (CPFE) is a unique disorder described in several case series of upper lobe emphysema associated with lower lobe fibrosis. Patients with this entity have relatively preserved lung volumes and spirometry but marked reductions in diffusing capacity on pulmonary function testing. Smoking appears to be the predominant risk factor for this disorder. Usual interstitial pneumonia has been the most common histological pattern of interstitial lung disease described on biopsy in the literature. OBJECTIVES: To characterize the clinical, imaging and pathological features of a cohort of patients with CPFE. METHODS: Retrospective review of electronic medical record data, radiological imaging, and available lung biopsy specimens for a series of 10 patients with CPFE at the Providence VA Medical Center, Providence, R.I., USA. RESULTS: We describe a series of 10 patients with CPFE. All had severe reductions in diffusing capacity out of proportion to their lung volumes and spirometry. All had predominantly upper lobe emphysema on computed tomography; 8/10 had lower lobe subpleural reticular abnormalities and honeycombing, while 2 had lower lobe ground glass changes on imaging. These 2 patients demonstrated a pattern of interstitial lung disease on biopsy characterized by intra-alveolar macrophage accumulation in association with marked alveolar septal fibrosis, consistent with a variant form of desquamative interstitial pneumonia with extensive fibrosis. CONCLUSIONS: The imaging findings and pathology in patients with CPFE are heterogeneous.