Low DLCO Research Articles

AB0614 Prognostic Factors of Functional Outcome in Systemic Sclerosis-Associated Interstitial Lung Disease

BackgroundInterstitial lung disease (ILD) is a frequent complication of systemic sclerosis (SSc) and is one of the first causes of mortality related to this disease. Screening sclerodermic patients for ILD...

AB0650 Autoantibody Profile in Systemic Sclerosis Associated Pulmonary Hypertension

BackgroundPulmonary hypertension (PH) is a severe complication of systemic sclerosis (SSc), affecting around 10% of patients. A recent meta-analysis showed an overall 3-year survival of 52%1. The impact of autoantibody...

Prediction of Pulmonary Complications and Long‐Term Survival in Systemic Sclerosis

To assess survival and incidence of organ-based complications in a large single-center cohort of unselected systemic sclerosis (SSc) patients, and to explore predictors of survival and clinically significant pulmonary fibrosis (PF) and pulmonary hypertension (PH). The study cohort consisted of 398 consecutive SSc patients, followed up for up to 15 years. Cox proportional hazards analysis with demographic, clinical, and laboratory characteristics as predictor variables was used to develop prediction models for pulmonary complications and survival. The overall survival estimate at the end of followup was 57% among patients with limited cutaneous SSc (lcSSc) and 50% among patients with diffuse cutaneous SSc (dcSSc) (P = 0.017). We found that greater age at disease onset, dcSSc, lower diffusing capacity for carbon monoxide (DLco), lower hemoglobin levels, higher serum creatinine levels, and the presence of PH or cardiac involvement were independent predictors of worse survival. Over the entire followup period, 42% of dcSSc patients and 22% of lcSSc patients developed clinically significant PF (P < 0.001). The variables that predicted clinically significant PF development were dcSSc, greater age at onset, lower forced vital capacity and DLco, and the presence of anti-topoisomerase I antibody, while the presence of anticentromere antibody was protective. There was no difference in cumulative incidence of PH between the 2 subsets-24% in lcSSc and 18% in dcSSc (P = 0.558). Incidence rates were 1-2% per year. The PH prediction model demonstrated that greater age at onset, increase in serum creatinine levels, lower DLco, and the presence of anti-RNA polymerase III or anti-U3 RNP antibodies were associated with increased risk of PH, while anti-topoisomerase I antibody positivity reduced the hazard. Our study provides data on long-term outcome of SSc and the timing and frequency of major organ complications. The predictive models we present could be used as clinical tools for patient risk stratification and could facilitate cohort enrichment for event-driven studies.

Development of pulmonary hypertension in a high-risk population with systemic sclerosis in the Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma (PHAROS) cohort study

ObjectivesPHAROS registry is a prospective longitudinal cohort study to understand the natural history of pulmonary hypertension (PH) in systemic sclerosis (SSc). Methods“At-risk” pulmonary arterial hypertension (PAH) is defined by these entry criteria: echocardiogram (echo) systolic pulmonary arterial pressure (sPAP) >40mmHg, diffusion lung capacity of carbon monoxide (DLco) <55% predicted, or ratio of percentage forced vital capacity (FVC)/percentage DLco >1.6, as measured by pulmonary function testing (PFT). Patients were followed up annually and right heart catheterization (RHC) performed if PH was suspected. We used descriptive statistics and Kaplan–Meier estimate of time to PH diagnosis. ResultsA total of 251 “at-risk” subjects were enrolled between 2005 and 2012 and followed up for mean of 2.5 ± 1.2 years. The mean age at entry was 56.7 ± 11.0 and disease duration was 9.9 ± 8.7 years.Overall, 82 patients had RHC, and 35 were confirmed to have new PH. There were no differences in age, gender, SSc subtypes, antibodies, and disease duration between the “at-risk” and new PH groups. Using Kaplan–Meier survival, the time to PH was 10% at 2 years, 13% at 3 years, and 25% at 5 years. Most new PH patients at entry met the PFT criteria (76%), had significantly higher sPAP (p = 0.013), had shorter 6-min walk distance, and had exercise-induced hypoxia (p = 0.003) than “at-risk” PAH group. ConclusionsA low DLco, high FVC/DLco, exercise-induced hypoxia and entry echo sPAP > 40 were strongly associated with future PH, though RHC was necessary to confirm PH. This ongoing prospective study confirms that these high-risk factors do predict future PH.

Lifetime occupational exposure to dusts, gases and fumes is associated with bronchitis symptoms and higher diffusion capacity in COPD patients.

BackgroundOccupational exposure to dusts, gases and fumes has been associated with reduced FEV1 and sputum production in COPD patients. The effect of occupational exposure on other characteristics of COPD, especially those reflecting emphysema, has not been studied in these patients.MethodsWe studied 338 patients hospitalized for a first exacerbation of COPD in 9 Spanish hospitals, obtaining full occupational history in a face-to-face interview; job codes were linked to a job exposure matrix for semi-quantitative estimation of exposure to mineral/biological dust, and gases/fumes for each job held. Patients underwent spirometry, diffusing capacity testing and analysis of gases in stable conditions. Quality of life, dyspnea and chronic bronchitis symptoms were determined with a questionnaire interview. A high- resolution CT scan was available in 133 patients.Results94% of the patients included were men, with a mean age of 68(8.5) years and a mean FEV1% predicted 52 (16). High exposure to gases or fumes was associated with chronic bronchitis, and exposure to mineral dust and gases/fumes was associated with higher scores for symptom perception in the St. George’s questionnaire. No occupational agent was associated with a lower FEV1. High exposure to all occupational agents was associated with better lung diffusion capacity, in long-term quitters. In the subgroup with CT data, patients with emphysema had 18% lower DLCO compared to those without emphysema.ConclusionsIn our cohort of COPD patients, high exposure to gases or fumes was associated with chronic bronchitis, and high exposure to all occupational agents was consistently associated with better diffusion capacity in long-term quitters.

A3.9 IGG subclasses of autoantibodies directed against the angiotensin receptor type 1 and the endothelin receptor type a and their clinical relevance

Background and ObjectivesIgG4-related diseases are often characterised by a generalised inflammatory fibrosis which is also present in patients suffering from systemic sclerosis (SSc). Recent findings indicate the importance of autoantibodies...

Idiopathic Pulmonary Fibrosis: New Insights to Functional Characteristics at Diagnosis

The lung function of patients with idiopathic pulmonary fibrosis (IPF) has not been characterized in detail. objective: To characterize the heterogeneous physiological abnormalities that exist in patients with IPF during their initial clinical evaluation. Lung function tests from 93 patients, performed within six months of the initial diagnosis of IPF, were obtained from a referral pulmonary function laboratory at a tertiary care hospital in Canada. A restrictive pattern was defined as total lung capacity (TLC) <95th percentile of predicted value. Patients with obstructive lung disease, lung cancer, emphysema and other restrictive lung diseases were excluded. On diagnosis, 73% of patients with IPF had a restrictive pattern, with a mean TLC of 72% of predicted. Mean forced vital capacity (FVC) was 71% and 44% of patients had an FVC <95th percentile. Mean diffusing capacity for carbon monoxide (DLCO) was 60% and DLCO⁄alveolar volume (VA) 92% of predicted. Increased severity of restriction - based on TLC - was associated with lower DLCO (74% of predicted in mild restriction and 39% of predicted in severe restriction) and higher forced expiratory volume in 1 s (FEV1)⁄FVC ratio (82% of predicted in mild restriction and 90% of predicted in severe restriction) but not with age (76 years in mild restriction and 69 years in severe restriction). Regardless of severity of restriction, the average DLCO⁄VA (≥86% of predicted) remained within normal limits. One in four patients with IPF had normal TLC and more than one-half had a normal FVC during initial evaluation. As the severity of the restriction increased, FEV1⁄FVC increased, DLCO decreased but DLCO⁄VA remained normal.

Lung diffusion capacity in children with respiratory symptoms and untreated GERD

BackgroundGastroesophageal reflux disease (GERD) is associated with many respiratory disorders, among which, chronic cough, laryngitis, and asthma are among the most common. We investigated lung function, including gas diffusion capacity, in children with poor asthma control or chronic laryngitis with untreated GERD.Material/MethodsA total of 71 children, aged 6–17 years, with chronic respiratory and other symptoms suggestive for GERD, were enrolled and divided into 2 groups: chronic laryngitis and asthma. Participants underwent 24-hour pH monitoring and lung function assessment, measurement of single-breath diffusing capacity of the lung for carbon monoxide (DLCO), and fraction of exhaled nitric oxide (FENO) measurement.Results24-hour pH monitoring was positive for GERD in 92.1% of preselected children with asthma and 90.1% of children with chronic recurrent laryngitis. All flows (PEF, MEF75, MEF50, and MEF25) were significantly lower in the asthma group, while FENO and DLCO were significantly lower in the laryngitis group. A significant inverse relationship was found between DLCO and all reflux indexes in the laryngitis group. Each unit change of Johnson-DeMeester score and Boix-Ochoa score increased the odds for significantly lower DLCO in laryngitis patients by 3.9% and 5.5%, respectively.ConclusionsIn children with uncontrolled asthma and chronic laryngitis, the regurgitation of gastric contents due to GERD contributes to poor asthma control and aggravation of chronic laryngitis. Despite having normal lung function, the gas diffusion capacity should be controlled in patients with GERD and chronic laryngitis, and it might be the very first abnormality in distal airways.

Severely reduced diffusion capacity in idiopathic pulmonary arterial hypertension: patient characteristics and treatment responses

A subgroup of patients with idiopathic pulmonary arterial hypertension (IPAH) has severely reduced diffusing capacity of the lung for carbon monoxide (DLCO) and poor prognosis. Their characteristics are currently unknown. The aim of this study is to contrast clinical characteristics and treatment responses of IPAH-patients with a severely reduced and more preserved DLCO. Retrospectively, 166 IPAH patients were included and grouped based on a DLCO cut-off value of 45% pred (IPAH(<45%) and IPAH(≥45%)). Clinical characteristics, treatment responses and survival were compared. IPAH(<45%) were older, more often male, had a more frequent history of coronary disease and a higher tobacco exposure. Forced expiratory volume in 1 s (FEV1), FEV1/forced vital capacity, total lung capacity and alveolar volume values were slightly lower and computed tomography scan abnormalities more prevalent in patients with a low DLCO. Age and number of pack years were independently associated with DLCO < 45% pred. IPAH(<45%) showed no different haemodynamic profile, yet worse exercise performance and a worse survival rate, which were both related to age, sex and the presence of coronary disease. To conclude, a severely reduced DLCO in IPAH is associated with advanced age and a greater tobacco exposure. These patients have a worse exercise performance despite a similar hemodynamic profile. We confirm the decreased survival in this patient group and now show that this poor outcome is related to age, sex and the presence of coronary disease.

Effects of guideline-oriented pharmacotherapy in patients with newly diagnosed COPD: a prospective study

Whether guideline-oriented pharmacotherapy prevents the decline in pulmonary function or reduces systemic inflammation associated with chronic obstructive pulmonary disease (COPD) is uncertain. The aim of this study was to assess the outcome of COPD in clinical practice under real-world conditions in Taiwan as measured by pulmonary function and systemic inflammation parameters (C-reactive protein (CRP) or white blood cell (WBC)) after initiation of guideline-oriented pharmacotherapy. Newly diagnosed COPD patients were enrolled and prospectively observed in real-world outpatient practice following initiation of pharmacotherapy of COPD. Pulmonary function, WBC and neutrophil counts, and CRP level of COPD patients were assessed annually. This study enrolled 566 patients and 263 returned for follow-up visits. Significantly higher postbronchodilator FVC, FEV1, and FEV1/FVC but lower DLCO were found at 1 year compared to baseline values. During 4-year follow-up period, FVC and FEV1 remained stable. DLCO progressively declined compared to baseline. No significant changes were seen in CRP and neutrophil count over a 3-year period. Values of CRP, WBC, and neutrophil count correlated inversely with FEV1, FVC, FEV1/FVC, and DLCO. Guideline-oriented pharmacotherapy of COPD improves airflow limitation but does not prevent the alveolar destruction and systemic inflammation under real-world conditions in Taiwan.

THU0221 Lung physiology impairment in anca-associated vasculitis (AASV)

BackgroundAlthough lung involvement in ANCA-associated vasculitis (AASV) is frequent, few studies1 exist regarding assessment of lung function.ObjectivesTo describe lung function in inactive AASV patients, relate them to previous lung damage...

AB0511 The analysis of prognostic factors in patients with inflammatory myopathies and amyopathic dermatomiositis complicated with interstitial lung disease

BackgroundBecause interstitial lung disease (ILD) is one of the most critical manifestations and can be lethal in inflammatory myopathies (IM), especially amyopathic dermatomiositis (ADM), it is important to determine prognostic...

OP0036 An Evidence-Based Tool for Detection of Pulmonary Arterial Hypertension in Systemic Sclerosis: The Detect Study

BackgroundDiagnosis of pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc) requires right heart catheterisation (RHC). Current screening recommendations are consensus-based and focus on echocardiography and symptoms. While false positives are...

Bone stiffness and failure load are related with clinical parameters in men with chronic obstructive pulmonary disease

Osteoporosis is frequently seen in patients with chronic obstructive pulmonary disease (COPD). Because research on bone structure and bone strength in COPD patients is limited, the objectives of this pilot study were as follows: (1) to compare bone structure, stiffness, and failure load, measured at the peripheral skeleton, between men with and without COPD after stratification for areal bone mineral density (aBMD); and (2) to relate clinical parameters with bone stiffness and failure load in men with COPD. We included 30 men with COPD (normal aBMD, n = 18; osteoporosis, n = 12) and 17 men without COPD (normal aBMD, n = 9; osteoporosis, n = 8). We assessed pack-years of smoking, body mass index (BMI), fat free mass index (FFMI), pulmonary function (forced expiratory volume in 1 second [FEV1 ], FEV1 /forced vital capacity [FVC], diffusion capacity for carbon monoxide [DLCO], and transfer coefficient for carbon monoxide [KCO]), and extent of emphysema. Bone structure of the distal radius and tibia was assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT), and bone stiffness and failure load of the distal radius and tibia were estimated from micro finite element analysis (µFEA). After stratification for aBMD and COPD, men with osteoporosis showed abnormal bone structure (p < 0.01), lower bone stiffness (p < 0.01), and lower failure load (p < 0.01) compared with men with normal aBMD, and men with COPD had comparable bone structure, stiffness, and failure load compared with men without COPD. In men with COPD, lower FFMI was related with lower bone stiffness, and failure load of the radius and tibia and lower DLCO and KCO were related with lower bone stiffness and failure load of the tibia after normalization with respect to femoral neck aBMD. Thus, this pilot study could not detect differences in bone structure, stiffness, and failure load between men with and without COPD after stratification for aBMD. FFMI and gas transfer capacity of the lung were significantly related with bone stiffness and failure load in men with COPD after normalization with respect to femoral neck aBMD.

Relationship between cardiac output via acetylene rebreathing and echocardiography in heart failure

Our lab has demonstrated a lower cardiac output (Q) in patients with heart failure (HF) vs. controls (CTL) using acetylene rebreathing (ACET). This technique may be dependent on lung health, which is altered in HF. Therefore, we examined the relationship between Q from echocardiography (echo) and Q from ACET at rest and during exercise. Additionally, we examined the relationship between stroke volume (SV) estimated from O2 pulse compared to SV by ACET (SVA). 26 controls (CTL) and 18 HF patients with preserved ejection fraction (EF) completed an exercise test on a cycle ergometer. Lung conductance was measured by lung diffusion for carbon monoxide (DLCO). Measures of Q (QA, Acetylene rebreathe; QE, transthoracic echo), heart rate (HR, 12‐lead ECG), and oxygen consumption (VO2, metabolic cart) were taken at rest and peak exercise. Stroke volume (SV) and O2 pulse were calculated as Q/HR and VO2/HR, respectively. HF patients had lower DLCO compared to CTL (Rest: DLCO=11±0.5 vs 14±0.6 ml/min/mmHg, p&lt;0.05). At rest and exercise, QE was moderately correlated with QA in CTL (Rest: r=0.47; Pk Ex: r=0.51, p&lt;0.05) and HF (rest: r=0.47; Pk Ex: r=0.77, p&lt;0.05). O2 pulse was significantly related to SVA at rest and exercise in CTL (Rest: r=0.76; Pk Ex: r=0.81, p&lt;0.05) and HF (Rest: r=0.81; Pk Ex: r=0.82, p&lt;0.05). Cardiac function assessed via ACET is related to cardiac function by echo and O2 pulse in patients with HF with preserved EF.

Quality of life as measured by the short-form 36 (SF-36) questionnaire in patients with early systemic sclerosis and undifferentiated connective tissue disease

ObjectiveTo investigate health-related quality of life (HRQOL) in patients affected by early systemic sclerosis (eSSc) and to compare it with that of patients with undifferentiated connective tissue disease (UCTD).MethodsAt baseline, 31 eSSc and 35 UCTD patients underwent clinical evaluation, laboratory investigations, nailfold videocapillaroscopy, echocardiography, and lung function tests. All patients and 40 controls, matched for sex and age completed the Short Form-36 (SF-36) questionnaire and the Health Assessment Questionnaire Disability Index (HAQ-DI).ResultsSF-36 scores were significantly lower in eSSc and UCTD patients than in healthy controls as regards the following domains: physical component score (PCS), mental component score (MCS), physical functioning, role-physical, bodily pain, general health and mental health. PCS was negatively correlated to the HAQ-DI (rho −0.59; p = 0.0004) and ESR >20 mm/h (rho −0.58; p = 0.0006) in eSSc patients. No statistically significant correlation was found between PCS, MCS and HAQ-DI in UCTD patients. Age, sex, disease duration, history of arthritis, low levels of either C3 or C4, a low DLCO (carbon monoxide lung diffusion) and inversion of the E/A ratio were not correlated to PCS and MCS in either eSSc or UCTD patients.ConclusionMany eSSc or UCTD patients perceive they have an impaired quality of life in both physical and mental domains. This condition has to be taken into account by the clinicians involved in the care of these patients.

Exercise-Induced Pulmonary Hypertension in Scleroderma Patients: A Common Finding but with Elusive Pathophysiology

The etiology of exercise-induced pulmonary hypertension (exPH) in systemic sclerosis (SSc) remains a complex task, as both left ventricle (LV) diastolic dysfunction and pulmonary vascular disease can contribute to its development. We determined the incidence of exPH in SSc and examined the association between pulmonary artery systolic pressure (PASP) and tissue Doppler-derived indexes of pulmonary capillary wedge pressure (PCWP). Thirty-eight patients with SSc were studied, using a cycloergometer protocol; 10 were excluded due to resting PH or absence of tricuspid regurgitation (TR); TR and mitral E-wave velocities, LV outflow tract time-velocity integral and LV septal E'-wave were measured before and in peak exercise to calculate cardiac output (CO), PCWP and pulmonary vascular resistance (PVR). Mean age of diagnosis was 57.9 ± 8.9 years. At a mean workload of 64 ± 29 Watts, 48% of patients increased PASP ≥ 50 mmHg. PCWP, assessed by the E/e' ratio, did not change significantly during exercise (10.2 ± 3.1-10.0 ± 5.1; P = NS). Only 3 patients had elevations of the E/e' ratio ≥ 13 during exercise; 2 of them had an exercise PASP ≥ 50 mmHg, yielding a proportion of exPH due to elevated LV filling pressures of 2/11 (18%). Patients with exPH had lower DLCO and had more frequently the diffuse SSc. The elevation of PASP during exercise in most patients of this cohort seems to be related to a reduced pulmonary vascular reserve, and not to an increase in PCWP. Further studies are warranted to determine the therapeutic, as well as prognostic implications of these findings.

S26 Individualising the Mortality Risk For Lung Volume Reduction Surgery

BackgroundDespite the positive results of the NETT trial in favour of lung volume reduction surgery (LVRS) uptake of the technique has been limited largely due to an exaggerated fear of...

Is There an Added Value of Cardiopulmonary Exercise Testing in Sarcoidosis Patients?

Cardiopulmonary exercise testing (CPET) with blood gas analysis may be helpful when there is a discrepancy between clinical findings and physiologic tests at rest. The aim of this study was to examine the added value of CPET compared to the measurement of the diffusing capacity of the lung for carbon monoxide (DLCO) in detecting impaired pulmonary gas exchange in sarcoidosis patients. The clinical records of 160 (age = 41.3 ± 10.0 years; number of females = 63) sarcoidosis patients referred to the former MUMC ild care center were retrospectively reviewed. Patients performed a symptom-limited incremental exercise test with blood gas analysis on a bicycle ergometer. DLCO was measured by the single-breath method. DLCO (mean = 83.2 ± 18.0 %) below 80 % of predicted was demonstrated by 38 % of the sarcoidosis patients in our sample. Of the patients with normal DLCO (n = 99, 61.9 %), the P(A-a)O(2) at maximal exercise [P(A-a)O(2)max] was moderately increased (>2.5 kPa) in 69.7 % and excessively increased (>4.7 kPa) in 18.2 %. Pulmonary gas exchange impairment (PGEI) was more obvious in patients with lower DLCO values. A DLCO value below 60 % of predicted indicated substantial gas exchange impairment. PaO(2) at rest, DLCO, and FVC as a percentage of predicted and radiographic staging predicted 40 % of the PGEI at maximal exercise. A substantial number of the symptomatic sarcoidosis patients with normal DLCO appeared to have PGEI at maximal exercise, suggesting that normal DLCO at rest is an inappropriate predictor of abnormal pulmonary gas exchange during exercise. CPET appeared to offer added value in detecting impaired gas exchange during exercise in sarcoidosis patients with unexplained disabling symptoms.

Impact of interstitial lung disease on short-term and long-term survival of patients undergoing surgery for non-small-cell lung cancer: analysis of risk factors

The study aimed to determine the impact of interstitial lung disease (ILD) on postoperative morbidity, mortality and long-term survival of patients with non-small-cell lung cancer (NSCLC) undergoing pulmonary resection. We performed a retrospective chart review of 775 consecutive patients who had undergone lung resection for NSCLC between 2000 and 2009. ILD, defined by medical history, physical examination and abnormalities compatible with bilateral lung fibrosis on high-resolution computed tomography, was diagnosed in 37 (4.8%) patients (ILD group). The remaining 738 patients were classified as non-ILD (control group). We also attempted to identify the predictive factors for early and late survival in patients with ILD following pulmonary resection. There was no significant difference between the two groups in terms of age (69 vs 66 years), sex (79 vs 72% male), smoking history (93 vs 90% smokers), forced expiratory volume in 1 s % of predicted (89 vs 84%), predicted values of forced vital capacity (FVC)% (92 vs 94%), types of surgical resection and histology. Patients with ILD had a higher incidence of postoperative acute respiratory distress syndrome (ARDS; 13 vs 1.8%, P < 0.01) and higher postoperative mortality (8 vs 1.4%, P < 0.01). The overall 5-year survival rate was 52% in the ILD and 65% in the non-ILD patients, respectively (P = 0.019). In the ILD group, at the median follow-up of 26 months (range 4-119), 19 (51%) patients were still alive and 18 (49%) had died in the ILD group. The major cause of late death was respiratory failure due to the progression of fibrosis (n = 7, 39%). In the ILD group, lower preoperative FVC% (mean 77 vs 93%, P < 0.01) and lower diffusing capacity of the lung for carbon monoxide (DLCO%; 47 vs 62%; P < 0.01) were significantly associated with postoperative ARDS. In conclusion, major lung resection in patients with NSCLC and ILD is associated with an increased postoperative morbidity and mortality. Patients with a low preoperative FVC% should be carefully assessed prior to undergoing surgery, particularly in the presence of a lower DLCO%. Long-term survival is significantly lower when compared with patients without ILD, but still achievable in a substantial subgroup. Thus, surgery can be offered to properly selected patients with lung cancer and ILD, keeping in mind the risk of respiratory failure during the evaluation of such patients.