Baseline Pulmonary Function Research Articles

Trajectories of caregiver burden in families of adult cystic fibrosis patients.

This was a longitudinal analysis of survey data obtained from caregivers of adult CF patients participating in an early intervention palliative care trial. Caregivers completed the validated Brief Assessment Scale for Caregivers (BASC) repeatedly over a 28-month period. Mixed-effects modeling evaluated multivariate associations with positive and negative caregiver perceptions over time. Of the 54 caregivers, 47.9% were spouses. The mean age was 50.9 years (SD = 13.2); 72.2% were women; 75.9% were married; and 63.0% were employed. At baseline, the BASC revealed large variations in positive and negative perceptions of caregiving. Although average scores over time were unchanging, variation was greater across caregivers than within caregivers (0.49 vs. 0.27, respectively). At baseline, the positive impact of caregiving in the sample was higher than the negative impact. Multivariate analysis revealed that patients' baseline pulmonary function and their full-time employment status predicted caregiver burden over time. Caregivers of CF patients varied in their positive and negative caregiving experiences, although burden levels in individual caregivers were stable over time. When the disease was advanced, caregivers of CF patients experienced more overall burden but also more positive impact. This suggests that the role of caregivers may become more meaningful as disease severity worsens. In addition, full-time patient employment was associated with lower caregiver burden regardless of disease severity. This suggests that burden in CF caregivers may be predicted by financial strain or benefits conferred by patient employment. These associations require further investigation to determine whether highly burdened caregivers can be identified and assisted using tailored interventions.

Ipilimumab and early signs of pulmonary toxicity in patients with metastastic melanoma: a prospective observational study.

Ipilimumab, an immune checkpoint inhibitor, is approved for treatment metastastic melanoma and is a promising agent against other malignancies. There is some preliminary evidence from case reports that ipilimumab treatment may be associated with pulmonary side effects. However, data from prospective studies on ipilimumab-related pulmonary toxicity are still scarce. Serial spirometries and measurements of CO-diffusion capacity (DLCO) in patients with metastatic melanoma before and during treatment with ipilimumab were performed. A reduction from baseline of forced vital capacity (FVC) of≥10%, or≥15% of DLCO was defined as clinically meaningful and indicative for pulmonary toxicity. Of 71 patients included in this study, a clinically meaningful lung function decline was registered in 6/65 (9%), 5/44 (11%), and 9/38 (24%) patients after 3, 6, and 9weeks of treatment initiation, respectively. Even after adjusting for age, concomitant melanoma treatment, progressive pulmonary metastases, and baseline pulmonary function values, mean±SD DLCO decreased significantly during follow-up (-4.3%±13.6% from baseline, p=0.033). Only 7% of patients reported respiratory symptoms. Clinically manifest ipilimumab-related pneumonitis was diagnosed only in one patient (1.4%). DLCO decline maybe an early indicator of subclinical pulmonary drug toxicity. Therefore, routine pulmonary function testing including DLCO measurement during treatment might help for risk stratification to screen for ipilimumab-related pneumonitis.

Subjective Global Assessment (SGA) Score Could Be a Predictive Factor for Radiation Pneumonitis in Lung Cancer Patients With Normal Pulmonary Function Treated by Intensity-Modulated Radiation Therapy and Concurrent Chemotherapy

IntroductionTo investigate the relationship between malnutrition and the severity of radiation pneumonitis (RP) in patients with lung cancer with normal baseline pulmonary function and lungs' V20 < 35% treated by intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy. Materials and MethodsA total of 150 patients with lung cancer who received definitive IMRT (≥ 60 Gy) and concurrent chemotherapy were enrolled. In the condition of normal baseline pulmonary function and strict constraints of the irradiation dose to normal lung tissues, we recorded Eastern Cooperative Oncology Group score; concurrent chemotherapy; clinical stage; the level of albumin (ALB), hemoglobin, and C-reactive protein; Subjective Global Assessment (SGA) scores; radiation esophagitis grade; V20 of lungs; and mean lung dose. These factors were correlated with RP using univariate and multivariate regression analyses. ResultsOf 150 patients, 12 patients (8.0%) developed Grade 3 to 5 RP, 37 (24.6%) patients developed grade 3 to 5 esophageal toxicity. In univariate analysis, ALB level (P = .002), radiation esophagitis (P < .001), and SGA score (P < .001) were significantly associated with RP. Multivariate analysis revealed that SGA (P < .001) was the independent predictor of RP. ConclusionsSGA could be a predictor for RP in patients with lung cancer treated with definitive IMRT and concurrent chemotherapy.

Objective Measurement of Adherence to Out-Patient Airway Clearance Therapy by High-Frequency Chest Wall Compression in Cystic Fibrosis.

Objective measures of adherence to high-frequency chest wall compression (HFCWC), a form of airway clearance therapy for patients with cystic fibrosis, are lacking. We used a novel electronic monitoring device integrated into an HFCWC vest to measure adherence compared with self-reported adherence. We determined factors that influenced adherence and how adherence correlated with baseline pulmonary function and pulmonary exacerbations. Data were collected by direct measurement of date, time of day, and duration of HFCWC use to determine the number of daily treatments and daily duration of treatments. Chart review provided prescribed airway clearance therapy treatment and demographic and clinical information. Subject and caregiver report of the daily number of airway clearance therapy treatments was obtained by telephone interviews. Analysis used 2-sample and paired t test, analysis of variance, and linear regression. Average adherence was 69%. Adherence was highest in children (82%, P = .02) and those receiving assistance with treatment (82%, P < .001). Subjects overestimated therapy duration from a mean ± SD of 127 ± 169% by adults to 19.2 ± 26.3% by parents or guardians of children. Average adherence decreased with increasing prescribed therapy time (P = .02). Average daily therapy time and adherence had significant positive associations with baseline FEV1 percent of predicted (P = .02 and P = .02, respectively) and negative associations with pulmonary exacerbations during the pre-study period and at baseline (P = .044 and P = .02, respectively). Greater adherence to HFCWC measured directly by a novel recorder was associated with better baseline pulmonary function and fewer exacerbations in the pre-study and baseline period. Adherence decreased with age and prescribed therapy time and increased with therapy assistance. Self-report overestimation is large and thus not an accurate measure of adherence.

SC08.01 Impact and Management of Co-Morbidities

SC08.01 Impact and Management of Co-Morbidities

Determining prognosis in acute exacerbation of COPD.

BackgroundAcute exacerbations are the leading causes of hospitalization and mortality in patients with COPD. Prognostic tools for patients with chronic COPD exist, but there are scarce data regarding acute exacerbations. We aimed to identify the prognostic factors of death and readmission after exacerbation of COPD.MethodsThis was a retrospective study conducted in the Department of Internal Medicine of Geneva University Hospitals. All patients admitted to the hospital with a diagnosis of exacerbation of COPD between 2008 and 2011 were included. The studied variables included comorbidities, Global Initiative for Chronic Obstructive Lung Disease (GOLD) severity classification, and biological and clinical parameters. The main outcome was death or readmission during a 5-year follow-up. The secondary outcome was death. Survival analysis was performed (log-rank and Cox).ResultsWe identified a total of 359 patients (195 men and 164 women, average age 72 years). During 5-year follow-up, 242 patients died or were hospitalized for the exacerbation of COPD. In multivariate analysis, age (hazard ratio [HR] 1.03, 95% CI 1.02–1.05; P<0.0001), severity of airflow obstruction (forced expiratory volume in 1 s <30%; HR 4.65, 95% CI 1.42–15.1; P=0.01), diabetes (HR 1.47, 95% CI 1.003–2.16; P=0.048), cancer (HR 2.79, 95% CI 1.68–4.64; P<0.0001), creatinine (HR 1.003, 95% CI 1.0004–1.006; P=0.02), and respiratory rate (HR 1.03, 95% CI 1.003–1.05; P=0.028) on admission were significantly associated with the primary outcome. Age, cancer, and procalcitonin were significantly associated with the secondary outcome.ConclusionCOPD remains of ominous prognosis, especially after exacerbation requiring hospitalization. Baseline pulmonary function remains the strongest predictor of mortality and new admission. Demographic factors, such as age and comorbidities and notably diabetes and cancer, are closely associated with the outcome of the patient. Respiratory rate at admission appears to be the most prognostic clinical parameter. A prospective validation is, however, still required to enable the identification of patients at higher risk of death or readmission.

Prognostic Significance of Pulmonary Function Test Abnormalities in Patients with Dyskeratosis Congenita

▪Introduction: Pulmonary fibrosis (PF) is a known complication in patients with dyskeratosis congenita (DC), reported in 15-20% of patients. PF is more common in older individuals with DC who may or may not have the classical clinical features of DC. PF in younger DC patients has been reported mainly in the setting of hematopoietic cell transplantation (HCT). There are no prospective studies of pulmonary function tests (PFT) in patients with DC.Objectives: To determine baseline pulmonary function status in patients with DC, association of PFT abnormalities with development or progression of pulmonary disease, and pulmonary outcomes in patients who did or did not receive HCT.Methods: DC patients older than 5 years of age underwent PFTs as part of a prospective IRB-approved cohort study at the NIH from 2002-2015. Data were obtained from spirometry [forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC)], lung volumes [total lung capacity (TLC)] and carbon monoxide diffusion capacity (DLCO). PFT abnormalities were classified as restrictive (normal FEV1/FVC and low TLC), obstructive (low FEV1/FVC and normal TLC) or mixed (low FEV1/FVC and low TLC) according to the American Thoracic Society Task Force guidelines. A low value was < lower limit of normal adjusted for age, sex, race and height. DLCO was also adjusted for hemoglobin. PFT data were analyzed in relation to the DC triad (nail dystrophy, skin pigmentation, leukoplakia), severe bone marrow failure (BMF needing treatment) and telomere length by flow FISH. Patients were followed through 2015. Pulmonary outcomes were compared in those with or without PFT abnormalities at evaluation and in those who did or did not receive HCT. P value <0.05 was significant.Results: Fifty-one patients with DC had PFTs, median age 19 yrs (range 6 - 69). Spirometry was abnormal in 16 patients (31%): 13 had restriction, 2 had obstruction, and 1 had a mixed pattern. DLCO was reduced (<80% of the predicted) in 32/49 patients (65%): 17 had mild (>60%), 13 had moderate (40-60%) and 2 had severely reduced (<40%) DLCO. All patients with abnormal spirometry had reduced DLCO compared with 18/35 (48%) with normal spirometry (p<0.0001). Patients with abnormal spirometry were more likely to have moderate/severe diffusion defects (10/16 vs 5/35; p=0.02), and severe BMF (12/16 vs 10/35; p=0.003) than those with normal spirometry. Telomere length and 2 or more features of the DC triad were not associated with PFT abnormality.Fourteen patients (27%) developed pulmonary disease at a median follow-up of 6 yrs (range 0.1 - 12 yrs) and a median age of 17 yrs (11 - 65): 10 had PF with interstitial honeycomb pattern on chest CT and 4 had pulmonary arteriovenous malformation (AVM) and mild fibrosis. Patients with abnormal spirometry and moderate/severely reduced DLCO were more likely to develop pulmonary disease than those with normal spirometry (12/16 vs 2/35; p<0.0001). Fourteen patients received a HCT (3 prior to and 11 after PFT evaluation) at a median age of 12 yrs (range 3 - 29). Eight of the 14 (57%) developed pulmonary disease 1 - 5 yrs after HCT (median 4 yrs) while 6/37 (16%) non-HCT patients developed PF (p=0.01). Transplanted patients developed pulmonary disease at a younger age than non-transplanted (median age 15 yrs, range 11 - 22 vs 54 yrs, 25 - 65; p=0.001), and had mutations in TINF2 (n=3), RTEL1, DKC1, WRAP53 (1 each); gene unknown (n=2). DC genes mutated in older non-HCT patients with PF were TERC (n=4), TERT (n=1), and unknown (n=1). The independent impact of severe DC phenotype, BMF, and HCT on pulmonary outcome could not be distinguished in young patients as most patients with severe disease had BMF and received HCT. There was no difference in PF among those who did or did not receive radiation for HCT. Four of the 10 deaths were due to PF.Conclusion: More than 30% of patients with DC have restriction and moderate/severe diffusion defect on PFTs, and these are more common in patients with severe BMF. PFT abnormalities are significantly associated with progression to PF, although they may also signal the presence of AVMs, a less common pulmonary manifestation of DC. PF in older patients is a known manifestation of the telomere biology disorder. It is unclear whether pulmonary disease in young patients is a feature of severe DC or the toxicity of HCT preparative regimens. Larger prospective studies are needed to confirm the predictive value of PFTs for future lung disease in patients with DC. DisclosuresNo relevant conflicts of interest to declare.

Validation of the prognostic value of MMP-7 in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive disease with poor prognosis and variable clinical course. Although matrix metalloproteinase-7 (MMP-7) is emerging as an important IPF biomarker, reproducibility across studies is unclear. We aimed to determine whether a previously reported prognostic threshold for MMP-7 was predictive of mortality in an independent cohort of IPF patients. MMP-7 concentrations obtained from heparinized plasma samples were determined by ELISA in 97 patients with IPF and 41 healthy controls. The association of the previously published heparin plasma MMP-7 threshold of 12.1 ng/mL with all-cause mortality or transplant-free survival (TFS) was determined, either as an independent biomarker or as part of the modified personal clinical and molecular mortality index (m-PCMI). MMP-7 plasma concentrations were significantly higher in IPF patients compared to healthy controls (14.40 ± 6.55 ng/mL vs 6.03 ± 2.51 ng/mL, P < 0.001). The plasma MMP-7 threshold of 12.1 ng/mL was significantly associated with both all-cause mortality and TFS (unadjusted Cox proportional hazard ratio (HR) = 25.85 and 15.49, 95% CI: 10.91-61.23 and 5.41-44.34, respectively, P < 0.001). MMP-7 concentrations, split by 12.1 ng/mL, were significantly (P < 0.05) predictive of mortality and TFS after adjusting for age, gender, smoking and baseline pulmonary function parameters, in a multivariate Cox proportional hazards model. MMP-7 concentrations were negatively correlated with diffusing lung capacity of carbon monoxide (DLCO ) (r = -0.21, P = 0.02), and positively with a mortality risk scoring system (GAP) that combines age, gender, forced vital capacity (FVC) and DLCO (r = 0.32, P = 0.001). This study confirms that MMP-7 concentrations could be used to accurately predict outcomes across cohorts and centres, when similar collection protocols are applied.

Exercise-induced bronchoconstriction update—2016

The first practice parameter on exercise-induced bronchoconstriction (EIB) was published in 2010. This updated practice parameter was prepared 5years later. In the ensuing years, there has been increased understanding of the pathogenesis of EIB and improved diagnosis of this disorder by using objective testing. At the time of this publication, observations included the following: dry powder mannitol for inhalation as a bronchial provocation test is FDA approved however not currently available in the United States; if baseline pulmonary function test results are normal to near normal (before and after bronchodilator) in a person with suspected EIB, then further testing should be performed by using standardized exercise challenge or eucapnic voluntary hyperpnea (EVH); and the efficacy of nonpharmaceutical interventions (omega-3 fatty acids) has been challenged. The workgroup preparing this practice parameter updated contemporary practice guidelines based on a current systematic literature review. The group obtained supplementary literature and consensus expert opinions when the published literature was insufficient. Asearch of the medical literature on PubMed was conducted, and search terms included pathogenesis, diagnosis, differential diagnosis, and therapy (both pharmaceutical and nonpharmaceutical) of exercise-induced bronchoconstriction or exercise-induced asthma (which is no longer a preferred term); asthma; and exercise and asthma. References assessed as relevant to the topic were evaluated to search for additional relevant references. Published clinical studies were appraised by category of evidence and used to document the strength of the recommendation. The parameter was then evaluated by Joint Task Force reviewers and then by reviewers assigned by the parent organizations, as well as the general membership. Based on this process, the parameter can be characterized as an evidence- and consensus-based document.

Plasma Vascular Endothelial Growth Factor Concentration and Alveolar Nitric Oxide as Potential Predictors of Disease Progression and Mortality in Idiopathic Pulmonary Fibrosis.

Background: Declining lung function signifies disease progression in idiopathic pulmonary fibrosis (IPF). Vascular endothelial growth factor (VEGF) concentration is associated with declining lung function in 6 and 12-month studies. Alveolar nitric oxide concentration (CANO) is increased in patients with IPF, however its significance is unclear. This study investigated whether baseline plasma VEGF concentration and CANO are associated with disease progression or mortality in IPF. Methods: 27 IPF patients were studied (maximum follow-up 65 months). Baseline plasma VEGF concentration, CANO and pulmonary function tests (PFTs) were measured. PFTs were performed the preceding year and subsequent PFTs and data regarding mortality were collected. Disease progression was defined as one of: death, relative decrease of ≥10% in baseline forced vital capacity (FVC) % predicted, or relative decrease of ≥15% in baseline single breath diffusion capacity of carbon monoxide (TLCO-SB) % predicted. Results: Plasma VEGF concentration was not associated with progression-free survival or mortality. There was a trend towards shorter time to disease progression and death with higher CANO. CANO was significantly higher in patients with previous declining versus stable lung function. Conclusion: The role of VEGF in IPF remains uncertain. It may be of value to further investigate CANO in IPF.

The objective evaluation of obstructive pulmonary diseases with spirometry

Airway obstruction is variable in asthma, while it is progressive and persistent in chronic bronchitis and emphysema. However, some of the patients presenting with symptoms of chronic airway diseases have clinical features of both asthma and COPD. The group with “Asthma–COPD Overlap Syndrome” (ACOS) phenotype was characterized by definitely irreversible airway obstruction accompanied by symptoms and signs of reversibility. In this study, we aimed to classify obstructive airway diseases by clinical, radiological, and pulmonary function tests. Patients at Samsun Medical Park Hospital Chest Diseases outpatient clinic were evaluated between January 2013 and April 2016, and a total of 235 patients were included in this study. Mean age of the patients was 55.3±14.5 (15–88) years, and the male/female ratio was 45/190. The baseline pulmonary function test results of the patients were as follows: mean forced vital capacity (FVC) values 2,825±1,108 (710–6,870) mL and 74.3±22.4 (24–155)%, forced expiratory volume in 1 second (FEV1) values 1,789±774 (480–4,810) mL and 58.1±20.0 (20–130)%, FEV1/FVC values 62.5±6.8 (39–70)%. Reversibility criteria following bronchodilator treatment were present in 107 (45.5%) patients. We specified five subgroups for patients according to their clinical, radiological, and pulmonary test findings, namely Group 1 (asthma), Group 2 (ACOS), Group 3 (chronic bronchitis), and Group 4 (emphysema). Additionally, a group of patients who had clinical and spirometric features of both asthma and chronic bronchitis in association with underlying emphysema (emphysema with chronic bronchitis and emphysema with asthma) was defined as the undifferentiated obstruction (UNDO) group. Number and percentage distribution of patients by groups were 58 (24.7%) in the asthma group, 70 (29.8%) in the ACOS group, 61 (26%) in the chronic bronchitis group, 32 (13.6%) in the emphysema group, and 14 (6%) in the UNDO group. In conclusion, in our study, the types of obstructive airway diseases could be classified based on clinical, radiological, and pulmonary function test findings into five groups, including asthma, ACOS, chronic bronchitis, emphysema, and both asthma and chronic bronchitis in association with underlying emphysema (emphysema with chronic bronchitis and emphysema with asthma) or the so-called undifferentiated obstruction. We suggest that these patient groups can be determined more accurately by studies that evaluate the association between spirometric FEV1, FEV1/FVC values, and reversibility ratios.

Chemosensitivity, Cardiovascular Risk, and the Ventilatory Response to Exercise in COPD.

COPD is associated with elevated cardiovascular risk and a potentiated ventilatory response to exercise. Enhanced carotid chemoreceptor (CC) activity/sensitivity is present in other clinical conditions, has been shown to contribute to sympathetic vasoconstrictor outflow, and is predictive of mortality. CC activity/sensitivity, and the resulting functional significance, has not been well examined in COPD. We hypothesized that CC activity/sensitivity would be elevated in COPD, and related to increased pulse wave velocity (a marker of CV risk) and the ventilatory response to exercise. Methods: 30 COPD patients and 10 healthy age-matched controls were examined. Participants performed baseline cardiopulmonary exercise and pulmonary function testing. CC activity was later evaluated by the drop in ventilation with breathing 100% O2, and CC sensitivity was then assessed by the ventilatory response to hypoxia (ΔVE/ΔSpO2). Peripheral arterial stiffness was subsequently evaluated by measurement of pulse wave velocity (PWV) using applanation tonometry while the subjects were breathing room air, and then following chemoreceptor inhibition by breathing 100% O2 for 2 minutes. Results: CC activity, CC sensitivity, PWV and the ventilatory response to exercise were all increased in COPD relative to controls. CC sensitivity was related to PWV; however, neither CC activity nor CC sensitivity was related to the ventilatory response to exercise in COPD. CC inhibition by breathing 100% O2 normalized PWV in COPD, while no effect was observed in controls. Conclusion: CC activity and sensitivity are elevated in COPD, and appear related to cardiovascular risk; however, CC activity/sensitivity does not contribute to the potentiated ventilatory response to exercise.

Marine Lipid Fraction Pcso-524™ (lyprinol®/omega-xl®) Of The New Zealand Green-lipped Mussel Does Not Improve Pulmonary And Respiratory Muscle Function In Non-asthmatic Elite Runners

Habitual endurance training may be associated with mild airway inflammation and subsequent deterioration in lung function. It has been shown that PCSO-524™ (Lyprinol®/Omega-XL®), a supplement extracted from the New Zealand green-lipped mussel (Perna canaliculus) comprising of up to 90 essential fatty acids, can moderate airway inflammation in humans with asthma, and in a murine-model of allergic airway disease. PURPOSE: To determine whether supplementation with PCSO-524™ (Lyprinol®/Omega-XL®) can improve pulmonary and respiratory muscle function in non-asthmatic elite runners. METHODS: 16 male, non-asthmatic elite runners participated in the study. Participants completed baseline resting pulmonary and respiratory muscle function testing, then were randomly assigned to either a treatment (PCSO-524™; 1 capsule contains 50 mg n-3 polyunsaturated fatty acids and 100 mg olive oil, n = 8) or placebo (1 capsule contains 100 mg olive oil; n = 8) group. During the supplementation period, subjects ingested 8 capsules of either treatment or placebo per day for 12 weeks. Following baseline testing, pulmonary and respiratory muscle function was assessed every two weeks throughout the 12 week supplementation period. RESULTS: Significant between-subjects main effects were not observed in forced vital capacity (FVC), forced expiratory volume in 1-second (FEV1.0), forced expiratory flow from 25-75% of lung volume (FEF25-75), peak expiratory flow (PEF), maximal voluntary ventilation (MVV), maximal inspiratory mouth pressure (PImax), maximal expiratory mouth pressure (PEmax), lung diffusion capacity (DLCO), and closing volume (CV) (all p > 0.05). A significant within-subjects main effect was observed in PEmax (p = 0.0242) and DLCO (p < 0.0001). No significant within-subject main effects were observed in FVC, FEV1.0, FEF25-75, PEF, MVV, PImax, and CV (all p > 0.05). A significant treatment by time interaction was observed in FEF25-75 (p = 0.0264) and DLCO (p = 0.0247), but no other significant interactions were observed (all p > 0.05). CONCLUSION: Supplementation with PCSO-524™ (Lyprinol®/Omega-XL®) does not improve pulmonary or respiratory muscle function in non-asthmatic elite runners.

Anti-Melanoma Differentiation-Associated Gene 5 Is Associated With Rapidly Progressive Lung Disease and Poor Survival in US Patients With Amyopathic and Myopathic Dermatomyositis.

Clinically amyopathic dermatomyositis (CADM) is a subset of dermatomyositis (DM) presenting with the characteristic rash of DM without objective muscle weakness. Asian studies report that anti-melanoma differentiation-associated gene 5 (anti-MDA-5) autoantibody in CADM is associated with interstitial lung disease (ILD), particularly rapidly progressive ILD (RPILD). These associations have not been established in US myositis patients. The goal of our study was to determine the association of anti-MDA-5 autoantibody with ILD, RPILD, and survival in US patients with CADM and classic DM. CADM patients were identified in the University of Pittsburgh Myositis Center Database and matched 1:1 (sex and age) to classic DM controls. Anti-MDA-5 was measured by serum enzyme-linked immunosorbent assay. Kaplan-Meier, log rank, and chi-square tests were used for analysis. We identified 61 CADM patients (62% women, mean age 48.2 years) and 61 classic DM controls (64% women, mean age 44.8 years). The frequencies of anti-MDA-5 positivity, ILD, and RPILD were similar in the 2 cohorts (MDA-5 positive: CADM 13.1% [8 of 61] and DM 13.1% [8 of 61], ILD positive: CADM 31.1% [19 of 61] and DM 26.2% [16 of 61], and RPILD positive: CADM 8.2% [5 of 61] and DM 5% [3 of 61]; P = 1, 0.55, and 0.46, respectively). Anti-MDA-5 positivity was significantly associated with ILD, since 50% of MDA-5-positive subjects (8 of 16) had ILD versus 25.5% of MDA-5-negative subjects (27 of 106; P = 0.04). Anti-MDA-5 was strongly associated with RPILD (P < 0.001). Anti-MDA-5-positive patients with ILD had worse baseline pulmonary function testing variables compared to anti-MDA-5-negative patients. Anti-MDA-5 positivity was significantly associated with poor survival (P = 0.007). Anti-MDA-5 antibody is significantly associated with ILD, RPILD, worse pulmonary outcome, and survival in US classic DM and CADM patients.

Serum uric acid as a marker of microvascular damage in systemic sclerosis patients

BackgroundMicrovascular damage of skin and internal organs is a hallmark of systemic sclerosis (SSc). Serum uric acid (UA) represents a marker of inflammation and endothelial dysfunction. The aims of this study were to evaluate the correlation between serum UA and intrarenal arterial stiffness evaluated by Doppler ultrasound in SSc patients with normal renal function. We also evaluated the correlation between serum UA and other clinical variables of the disease. MethodsForty-five SSc patients underwent clinical assessment, Doppler ultrasound of intrarenal arteries with evaluation of resistive index (RI), pulsatile index (PI), and systolic/diastolic ratio (S/D), echocardiography with systolic pulmonary artery pressure (PAPs), baseline pulmonary function tests, and nailfold videocapillaroscopy (NVC). In all patients serum UA was measured. ResultsThe serum UA showed a significant positive correlation with sCr (r=0.33, p<0.0001) and PAPs (r=0.38, p<0.01) >and negative correlation with CKD-EPI (r=−0.35, p<0.01). The mean value of serum UA increased with severity of NVC damage. Using this cut-off value of 4.7mg/dl, the mean value of Doppler indices of intrarenal stiffness is significantly different (p<0.05) in SSc patients with low normal or high normal serum UA. ConclusionsSerum UA concentration is higher in patients with high microvascular damage than in patients with low microvascular damage. These preliminary data must be confirmed in large prospective studies.

Assessment of Speckle-Tracking Echocardiography-Derived Global Deformation Parameters During Supine Exercise in Children.

Exercise echocardiography is an underutilized tool in pediatrics with current applications including detecting segmental wall abnormalities, assessing the utility of global ventricular function, and measuring pulmonary hemodynamics. No prior study has applied speckle-tracking echocardiography (STE) during exercise echocardiography in children. The aim of this study was to determine the feasibility of measuring speckle-tracking-derived peak systolic velocities, global longitudinal and circumferential strain, and global strain rates at various phases of exercise. Ninety-seven healthy children underwent cardiopulmonary exercise testing using supine cycle ergometry. The exercise stress test consisted of baseline pulmonary function testing, monitoring of blood pressure and heart rate responses, electrocardiographic recordings, and oxygen saturations while subjects pedaled against a ramp protocol based on body weight. Echocardiographic measurements and specifically speckle-tracking analysis were performed during exercise at baseline, at a heart rate of 160 beats per minute and at 10 min after exercise. Peak systolic velocity, peak systolic strain, and peak systolic strain rate at these three phases were compared in the subjects in which all measurements were accurately obtained. We were able to complete peak velocity, strain, and strain rate measurements in all three exercise phases for 36 out of the 97 subjects tested. There was no significant difference between the feasibility of measuring circumferential versus longitudinal strain (p = 0.25, B-corrected = 0.75). In the 36 subjects studied, the magnitude of circumferential strain values decreased from -18.3 ± 4.8 to -13.7 ± 4.0 % from baseline to HR 160 (p < 0.0001, B-corrected < 0.0001), before returning to -19.6 ± 4.4 % at recovery (p = 0.19 when compared to baseline). Longitudinal strain did not vary significantly from baseline to HR 160 (from -17.7 ± 4.4 to -16.6 ± 4.4 %, p = 0.16); likewise the average recovery strain was no different from those values (-18.4 ± 3.6 %; p = 0.34). Peak circumferential and longitudinal strain rates increased from baseline to HR 160, but neither decreased to baseline levels after 10 min of recovery, which correlated with heart rate variations with exercise. We studied the effects of frame rate on deformation measurements and we observed no difference between measurements taken at lower (<60 frames per second, fps) and higher (≥60 fps) frame rates. This study shows that it is technically difficult to retrospectively measure peak velocities, strain, and strain rate in exercising pediatric subjects with STE. The majority of subjects that were excluded from the study had inadequate echocardiographic images when tachycardic from increased respiratory effort and body movements near peak exercise. Improvements in technique and higher image frame rates could make application of STE to pediatric cardiopulmonary testing more successful in the future.

Lower Airway Obstruction Is Associated with Increased Vaso-Occlusive Pain Episodes in Adults with Sickle Cell Anemia

Background: Vaso-occlusive pain episodes (VOE) are the most common complication and reason for hospital admission in individuals with Sickle Cell Anemia (SCA). Recently our team demonstrated that in adults with SCA followed prospectively for approximately 5 years, a lower baseline Forced Expiratory Volume in 1 second percent predicted (FEV1%), which is associated with earlier mortality, but evidence of obstructive or restrictive lung function patterns is not (Blood 2015, in press). Based on the evidence that abnormal pulmonary function is associated with earlier mortality, we tested the hypothesis that baseline pulmonary function patterns were associated with SCA-related morbidity, including VOE and acute chest syndrome (ACS) events.Procedure: A prospective cohort of adults with SCA followed in the Cooperative Study for Sickle Cell Disease (CSSCD) was constructed based on a planned secondary analysis. Data from the first PFT record at age 21 and older were used for this study. Percent predicted values were determined for each participant based on their age, gender, height, and race for FEV1 and the ratio of FEV1 to forced vital capacity (FEV1/FVC) using the Global Lung Function 2012 equations (Eur Respir J, 2012; 40(6): 1324-1343). Assessment of lower airway obstruction was based on % predicted FEV1/FVC. Percent predicted total lung capacity (TLC), a measure of restrictive lung disease, was determined using published equations and corrected based on race. All PFT evaluations were checked for quality. Negative binomial regression models were used to determine the association between future VOE, ACS events, and spirometry measurements after adjusting for age, sex, hemoglobin, and fetal hemoglobin levels.Results: A total of 430 adults with SCA were evaluated. Ages of the study participants ranged from 21.7-66.4 years with a median age of 32.6 years at the time of first PFT and median follow-up was 5.5 years. Only FEV1/FVC% predicted as a continuous covariate was a significant predictor of future VOE. Lower FEV1/FVC% predicted was associated with higher future pain event rates with a rate ratio of 1.022 (95% CI 1.002 - 1.042; p=0.028). For every 10% decrease in FEV1/FVC% predicted there is a 23% increase in the rate ratio. TLC% predicted did not predict future VOE (p=0.762). FEV1/FVC% predicted or TLC% predicted did not predict future ACS events (p=0.618 and p=0.430 respectively). When FEV1/FVC% predicted and TLC% predicted < 5th percentile were used in the regression equation instead of continuous values, neither abnormal lung function parameter was associated with an increased incidence of VOE or ACS events.Conclusions: For the first time, we have demonstrated that spirometry evaluation with FEV1/FVC% predicted, as a measure of lower airway obstruction, identifies a group of adults with SCA at increased risk for future vaso-occlusive pain episode.Table 1CovariateRate Ratio (95% CI)PAge at PFT*-.112 (.850, .941).000Male1.032 (.581, 1.836).914Average Fetal Hemoglobin.985 (.894, 1.085).754Average Hemoglobin.954 (.763, 1.193).682Negative FEV1/FVC percent predicted**.022 (1.002, 1.042).028Final Negative Binomial Regression model for vaso-occlusive pain episodes after lung function testing (N= 430)*PFT is Pulmonary Function Test** Negative FEV1/FVC percent is reverse-coded so that lower values are associated with rate ratios above 1. DisclosuresNo relevant conflicts of interest to declare.

Changes in Pulmonary Function Following Image-Guided Stereotactic Lung Radiotherapy: Neither Lower Baseline Nor Post-SBRT Pulmonary Function Are Associated with Worse Overall Survival

To determine changes in pulmonary function brought about by lung stereotactic body radiation therapy (SBRT). One hundred and twenty-seven patients were treated with lung SBRT using 48 to 60Gy in four to five fractions on a prospective trial. We obtained pulmonary function tests (PFTs) at baseline, 6 weeks, 3 months, 6 months, 9 months, 12 months, and 24 months after SBRT. Group mean PFT parameter values are reported. At baseline forced expiratory volume in 1 second (FEV1) was 1.5 l (67% predicted, range: 0.4-3.4 l), corrected diffusing capacity for carbon monoxide was 12.2 ml/min/mmHg (50.8% predicted, range: 3.3-27.2 ml/min/mmHg), and total lung capacity was 5.7 l (102.4% predicted, range: 3.1-9.1 l). At 12 months, there was decline in FEV1 (-4.1%; p = 0.01), corrected diffusing capacity for carbon monoxide (-5.2%; p = 0.027), forced vital capacity (-5.7%; p = 0.004), and total lung capacity (-3.6%; p = 0.039). Declines in FEV1 (-7.6%; p = 0.001) and forced vital capacity (-8.9%; p = 0.001) persisted at 24 months. Rates of pneumonitis were 3.1% and 0.8% for grades 2 and 3, respectively. There were no grade 3 PFT toxicities at 12 months. Lower PFTs at baseline and 1 year after SBRT did not predict for worse overall survival. As the largest cohort of patients with prospective follow-up PFT evaluation after lung SBRT, this supports the safety of SBRT in this population of predominantly medically inoperable patients. While statistically significant, nearly all declines in PFTs would be rated as a grade 1 on the Radiation Therapy Oncology Group scale, demonstrating safety. PFT declines were not associated with worse overall survival.

Stereotactic body radiotherapy for early stage lung cancer: History and updated role.

Stereotactic Body Radiotherapy (SBRT) represents a consolidated treatment option for patients with medically inoperable early stage non-small cell lung cancer (NSCLC). The clinical evidence accumulated over the past decade supports its use as an alternative to surgery with comparable survival outcomes. Due to its limited toxicity, SBRT is also applicable to elderly patients with very poor baseline pulmonary function or other severe comorbidities. Recent comparative studies in operable patients raised the issue of the possible use of SBRT also for this subgroup, with quite promising results that still should be fully confirmed by prospective trials with long-term follow up. In early stage lung cancer, clinicians are now faced with a decision-making process that should take into account different factors. The need of pathological diagnosis and accurate nodal staging still represents a challenge, as well as the interpretation of radiological findings after SBRT, often confusing du to the difficulties in distinguishing between radiation-induced changes and local relapse. Aim of this review is to summarize and discuss the major studies on SBRT for early stage lung cancer, providing data on its efficacy and toxicity and discussing the still open issues on its role. Quality of life, pulmonary function and risk of secondary cancers are also discussed, as well as future perspectives and current research topics.

Oscillatory Positive Expiratory Pressure in Chronic Obstructive Pulmonary Disease

Evidence-based guidance for the use of airway clearance techniques (ACT) in chronic obstructive pulmonary disease (COPD) is lacking in-part because well-established measurements of pulmonary function such as the forced expiratory volume in 1s (FEV1) are relatively insensitive to ACT. The objective of this crossover study was to evaluate daily use of an oscillatory positive expiratory pressure (oPEP) device for 21–28 days in COPD patients who were self-identified as sputum-producers or non-sputum-producers.COPD volunteers provided written informed consent to daily oPEP use in a randomized crossover fashion. Participants completed baseline, crossover and study-end pulmonary function tests, St. George's Respiratory Questionnaire (SGRQ), Patient Evaluation Questionnaire (PEQ), Six-Minute Walk Test and 3He magnetic resonance imaging (MRI) for the measurement of ventilation abnormalities using the ventilation defect percent (VDP).Fourteen COPD patients, self-identified as sputum-producers and 13 COPD-non-sputum-producers completed the study. Post-oPEP, the PEQ-ease-bringing-up-sputum was improved for sputum-producers (p = 0.005) and non-sputum-producers (p = 0.04), the magnitude of which was greater for sputum-producers (p = 0.03). There were significant post-oPEP improvements for sputum-producers only for FVC (p = 0.01), 6MWD (p = 0.04), SGRQ total score (p = 0.01) as well as PEQ-patient-global-assessment (p = 0.02). Clinically relevant post-oPEP improvements for PEQ-ease-bringing-up-sputum/PEQ-patient-global-assessment/SGRQ/VDP were observed in 8/7/9/6 of 14 sputum-producers and 2/0/3/3 of 13 non-sputum-producers. The post-oPEP change in 3He MRI VDP was related to the change in PEQ-ease-bringing-up-sputum (r = 0.65, p = 0.0004) and FEV1 (r = –0.50, p = 0.009).In COPD patients with chronic sputum production, PEQ and SGRQ scores, FVC and 6MWD improved post-oPEP. FEV1 and PEQ-ease-bringing-up-sputum improvements were related to improved ventilation providing mechanistic evidence to support oPEP use in COPD. Clinical Trials # NCT02282189 and NCT02282202.