Trends In Lung Function Research Articles

Comment on: Antibody predictors of mortality and lung function trends in myositis spectrum interstitial lung disease.

Comment on: Antibody predictors of mortality and lung function trends in myositis spectrum interstitial lung disease.

Comment on: Antibody predictors of mortality and lung function trends in myositis spectrum interstitial lung disease: Reply.

Comment on: Antibody predictors of mortality and lung function trends in myositis spectrum interstitial lung disease: Reply.

Antibody predictors of mortality and lung function trends in myositis spectrum interstitial lung disease.

The impact of autoantibody profiles on prognosis of idiopathic inflammatory myositis associated interstitial lung disease (IIM-ILD) and myositis spectrum ILD with Myositis Specific Antibodies (MSA) remains unclear. This retrospective cohort study examines whether serological profiles are associated with mortality and longitudinal lung function change. Baseline clinical/demographic characteristics and follow-up lung function of consecutive adult patients with IIM-ILD or Interstitial Pneumonia with Autoimmune Features (IPAF) positive for MSAs were extracted from three hospitals. Univariate and multi-variate Cox-Proportional Hazards analyses were used to compare mortality between autoantibodies. Regression models were used to analyse lung function trends. Of 430 included patients, 81% met IIM criteria, 19% were IPAF-MSA. On univariate analysis, risk factors associated with mortality included higher age, Charlson Co-morbidity Index and CRP; and lower BMI, baseline TLCO% and FEV1%. Compared to anti-MDA5-negativity, anti-MDA5-positivity (MDA5+) was associated with high mortality in the first 3 months (HR 65.2. 95%CI 14.1, 302.0), while no significant difference was seen thereafter (HR 0.55, 95%CI 0.14, 2.28). On multi-variate analysis, combined anti-synthetase antibodies carried a reduced risk of mortality (HR 0.63), although individually, mortality was reduced in anti-Jo1 + (HR 0.61, 95%CI 0.4-0.87) and increased in anti-PL7+ patients (HR 2.07, 95%CI 1.44-2.99). Anti-MDA5+ was associated with slow improvement in %FVC over the first 3 years, while anti-PL7+ was linked with a slow decline from 12 months onwards. Among autoantibody profiles in myositis spectrum disorders, anti-MDA5+ and anti-PL7+ confer higher mortality risks. Survivors of an early peak of mortality in anti-MDA5+ disease appear to have a favourable prognosis.

181 Estimating personalized lung function trends from routine clinical care to facilitate analysis of daily data capture using remote technologies

181 Estimating personalized lung function trends from routine clinical care to facilitate analysis of daily data capture using remote technologies

Nationwide indoor smoking ban and impact on smoking behaviour and lung function: a two-population natural experiment

IntroductionMany countries have implemented indoor smoking bans over the past two decades. Although smoking bans have been shown to reduce cardiovascular outcomes, little is known about their impact on respiratory...

Monocyte and neutrophil levels are potentially linked to progression to IPF for patients with indeterminate UIP CT pattern

RationaleIdiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease with poor prognosis. Identifying patients early may allow intervention which could limit progression. The ‘indeterminate for usual interstitial pneumonia’ (iUIP)...

Does peripheral blood eosinophil count predict lung function improvement in adult subjects with asthma?

Previous studies have investigated the contribution of the eosinophilic phenotype, as defined by the peripheral blood eosinophil count, in predicting asthma outcomes. There is evidence that the eosinophilic phenotype predicts uncontrolled symptoms and asthma exacerbations.1,2 We are aware of no prospective study evaluating whether the eosinophilic phenotype is a useful biomarker for predicting lung function trends in subjects with asthma who have used maintenance therapy. This is an important issue, because predicting loss of lung function is a meaningful goal of asthma monitoring, as lung function decline leads to irreversible airway obstruction and worse clinical outcomes.

A pilot study of cystic fibrosis exacerbation response phenotypes reveals contrasting serum and sputum iron trends

The cystic fibrosis (CF) community seeks to explain heterogeneous outcomes of pulmonary exacerbation (PEX) treatment. Serum and sputum inflammatory mediators may identify people with CF (PwCF) at risk for suboptimal responses. However, lack of an established association between response phenotypes and these mediators limits clinical application. In this pilot study, we prospectively characterized treatment response phenotypes by assessing health-related quality-of-life (HRQoL) during PEX. We also measured lung function and iron-related biochemical parameters in serum and sputum. We classified subjects as sustained symptom-responders (SRs) or non-sustained symptom-responders (NSRs) based on the absence or presence, respectively, of worsened symptom scores after initial improvement. We used linear mixed models (LMMs) to determine whether trends in lung function, hematologic, serum, and sputum indices of inflammation differed between response cohorts. In 20 PwCF, we identified 10 SRs and 10 NSRs with no significant differences in lung function at PEX onset and treatment durations. SRs had better model-predicted trends in lung function than NSRs during PEX. Non-linear trends in serum and sputum iron levels significantly differed between SRs and NSRs. In adults with cystic fibrosis, PEX treatment response phenotypes may be correlated with distinctive trends in serum and sputum iron concentrations.

Cystic fibrosis with non-G551D gating mutations in Italy: Epidemiology and clinical characteristics.

Cystic fibrosis transmembrane conductance regulator (CFTR) gating mutations (GMs) result in CFTR that is present at the cell surface but nonfunctional. Patients with the G551D mutation, the most prevalent worldwide, have been well studied. Italian GM patients have mainly non-G551D mutations. We studied their epidemiology and clinical characteristics in the period spanning the pre/post ivacaftor introduction to the Italian market. Data from the Italian CF Registry were used to describe patients with GMs and compare them with F508del homozygous (F/F) patients. In total, 186 patients with GMs (median [range] age, 21.96 [0.13-63.38] years) were identified among the 5552 patients included in the study (3.3%). They had lower sweat chloride values at diagnosis than the F/F and a lower ratio of males. In the GM group, examining the data of the years 2012 and 2017 and comparing with F/F, lung infection by Staphylococcus aureus and diabetes became less prevalent, and better FEV1 and nutritional status were observed in 2017. The cross-sectional evaluation year-by-year from 2012 to 2017 of the GM group showed improving trends in lung function and body mass index, and the decreasing prevalence of diabetes compared with F/F. Longitudinal evaluation of GM patients showed improvement in percent predicted (pp)FEV1 and nutrition in the 2012-2017 period. These variations correspond to the introduction of treatment with the CFTR potentiator ivacaftor (2014/2015). Italian patients with GMs are few and are characterized by milder phenotypes than F/F patients. Improved outcomes are likely influenced by treatment with ivacaftor.

New treatment paradigms for connective tissue disease-associated interstitial lung disease.

Interstitial lung disease (ILD) is frequently observed in connective tissue disease (CTD) and is a major cause of mortality. In CTD-ILD, a marked variability in morphological patterns, time course and severity exists. In many patients, CTD-ILD is limited and inherently stable, although a significant proportion of patients have progressive disease. We review the utility of integration of the recently proposed disease behavior classification into the management of CTD-ILD, and recent advances in treatment approaches. Recent studies on scleroderma-ILD (SSc-ILD) staging and short-term lung function trends provide important information, although accurate prognostic markers, particularly in limited/early CTD-ILD, are still needed. Most patients with progressive CTD-ILD stabilize on immunosuppression, as observed in recent SSc-ILD trials and CTD-ILD retrospective series. A minority of patients present with life-threatening acute/subacute ILD, requiring intense immunosuppression, with limited available guidance. A significant minority of CTD-ILD patients have progressive disease despite immunosuppression. Ongoing trials with antifibrotic agents and with biologic agents may reveal a potential role for their use/addition. Ultimately, further research into the mechanisms linking autoimmunity to fibrosis and randomized controlled clinical trials are needed, with the aim of preventing irreversible damage of lung tissue, while minimizing burden of treatment.

Individualized lung function trends in alpha-1-antitrypsin deficiency: a need for patience in order to provide patient centered management?

BackgroundChronic obstructive pulmonary disease (COPD) is characterized by fixed airflow obstruction and accelerated decline of forced expired volume in 1 second (FEV1). Alpha-1-antitrypsin deficiency is a genetic cause of COPD and associated with more rapid decline in lung function, even in some never smokers (NS) but the potential for individualized assessment to reveal differences when compared to group analyses has rarely been considered.MethodsWe analyzed decline in post-bronchodilator FEV1 and gas transfer (% predicted) over at least 3 years (mean= 6.11, 95% CI 5.80–6.41) in our unique data set of 482 patients with alpha-1-antitrypsin deficiency (PiZ) to determine individual rates of decline, implications for prognosis, and potential clinical management.FindingsThere was a marked variation in individual rates of FEV1 decline from levels consistent with normal aging (observed in 23.5% of patients with established COPD, 57.5% of those without) to those of rapidly declining COPD. Gas transfer did not decline in 12.8% of NS and 20.7% of ex-smokers with established COPD (33.3% and 25.0%, respectively, for those without COPD). There was no correlation between decline in gas transfer and FEV1 for those with COPD, although a weak relationship existed for those without (r=0.218; P<0.025).ConclusionThese data confirm differing individual rates of lung function decline in alpha-1-antitrypsin deficiency, indicating the importance of comprehensive physiological assessment and a personalized approach to patient management.

Individual FEV1 Trajectories Can Be Identified from a COPD Cohort

Objective: We aim to make use of clinical spirometry data in order to identify individual COPD-patients with divergent trajectories of lung function over time. Study Design and Setting: Hospital-based COPD cohort (N = 607) was followed on average 4.6 years. Each patient had a mean of 8.4 spirometries available. We used a Hierarchical Bayesian Model (HBM) to identify the individuals presenting constant trends in lung function. Results: At a probability level of 95%, one third of the patients (180/607) presented rapidly declining FEV1 (mean -78 ml/year, 95% CI -73 to -83 ml) compared to that in the rest of the patients (mean -26 ml/year, 95% CI -23 to -29 ml, p ≤ 2.2 × 10-16). Constant improvement of FEV1 was very rare. The rapid decliners more frequently suffered from exacerbations measured by various outcome markers. Conclusion: Clinical data of unique patients can be utilized to identify diverging trajectories of FEV1 with a high probability. Frequent exacerbations were more prevalent in FEV1-decliners than in the rest of the patients. The result confirmed previously reported association between FEV1 decline and exacerbation rate and further suggested that in clinical practice HBM could improve the identification of high-risk individuals at early stages of the disease.

125 Feasibility of carrying out spirometry in 3 and 4 year old children in a standard clinic setting

Objectives: We used to introduce spirometry to 5 year old (yo) children with the aim of having reliable results by the age of 6. In 2009 we attempted this with 4yos. In 2011 a 2.5yo girl was keen to copy her 4yo sibling so was allowed to try spirometry simply to avoid conflict. Since she made a reproducible effort we decided to attempt this in all 3yos. Methods: Spirometry was carried out in clinic by the physiotherapist who knew which blowing techniques the children had learned during airway clearance, such as bubble PEP. A CareFusion MicroLab spirometer was used with the child incentive. Children aged 3 with good comprehension attempted the test. The parents understood the potential unreliability of the test. The children were asked to perform one long blow similar to blowing out birthday candles. The reaction of the incentive cartoon was explained. The flow-volume loop was checked between blows and further explanation given if necessary. The best of 3 attempts was recorded. Results: Some children took a second breath and others did not complete the blow, particularly after the incentive was met. During successive visits this usually improved. Overall 9 of 10 3−4yos produced reproducible results, 5 of whom had useful results at age 3. Several children have had these repeated on multiple clinic visits showing good lung growth with age. Conclusion:We have demonstrated that it is feasible during normal appointments to undertake reproducible spirometry in a significant proportion of children as young as 3. With the new global lung initiative normal ranges extending to younger age groups we will be able to make an earlier start in following individual trends in lung function.

126 What factors determine lung function decline in Polish CF children?

Objectives: We used to introduce spirometry to 5 year old (yo) children with the aim of having reliable results by the age of 6. In 2009 we attempted this with 4yos. In 2011 a 2.5yo girl was keen to copy her 4yo sibling so was allowed to try spirometry simply to avoid conflict. Since she made a reproducible effort we decided to attempt this in all 3yos. Methods: Spirometry was carried out in clinic by the physiotherapist who knew which blowing techniques the children had learned during airway clearance, such as bubble PEP. A CareFusion MicroLab spirometer was used with the child incentive. Children aged 3 with good comprehension attempted the test. The parents understood the potential unreliability of the test. The children were asked to perform one long blow similar to blowing out birthday candles. The reaction of the incentive cartoon was explained. The flow-volume loop was checked between blows and further explanation given if necessary. The best of 3 attempts was recorded. Results: Some children took a second breath and others did not complete the blow, particularly after the incentive was met. During successive visits this usually improved. Overall 9 of 10 3−4yos produced reproducible results, 5 of whom had useful results at age 3. Several children have had these repeated on multiple clinic visits showing good lung growth with age. Conclusion:We have demonstrated that it is feasible during normal appointments to undertake reproducible spirometry in a significant proportion of children as young as 3. With the new global lung initiative normal ranges extending to younger age groups we will be able to make an earlier start in following individual trends in lung function.

Accuracy of Individual Variables in the Monitoring of Long-term Change in Pulmonary Sarcoidosis as Judged by Serial High-Resolution CT Scan Data

In pulmonary sarcoidosis, the optimal means of quantifying change is uncertain. The comparative usefulness of simple lung function trends and chest radiography remains unclear. We aimed to explore and contrast the disease-monitoring strategies of serial pulmonary function tests (PFTs) and chest radiography compared against morphologic change on high-resolution CT (HRCT) scan. Seventy-three patients with sarcoidosis were identified who had two HRCT scans with concurrent chest radiography and PFTs. Chest radiography and HRCT scans were assessed by two radiologists for change in disease extent. Concordance between the scoring systems, as well as agreement between PFT trends (% change from baseline in FEV, FVC, and diffusing capacity of the lung for carbon monoxide [Dlco]), chest radiography, and chest HRCT scan change, were examined using the weighted κ coefficient of variation (Kw). There was fair agreement between change in extent of disease on chest radiograph and significant PFT trends (Kw = 0.35, P &lt; .001) and moderate agreement between change in extent of disease on serial HRCT scan and significant PFT trends (Kw = 0.64, P &lt; .0001). The integration of Dlco trends did not improve concordance between change on HRCT scan and PFT change. Change in gas transfer coefficient (ie, Dlco/alveolar volume) displayed no overall linkage with change in disease extent on chest radiograph (Kw = 0.07, P = .27) and only poor agreement with change in disease extent on HRCT scan (Kw = 0.17, P = .07). Significant PFT trends correlate better with morphologic change as defined by serial HRCT scan than extent of disease on radiograph. Isolated change in gas transfer coefficient is more frequently discordant with change in disease extent on chest radiograph and HRCT scan and may suggest a pulmonary vascular component.

Serum insulin-like growth factor-1 (IGF-1) during CF pulmonary exacerbation: Trends and biomarker correlations

Cystic fibrosis (CF) is characterized by low circulating levels of insulin-like growth factor-1 (IGF-1), a hormone produced by the liver that governs anabolism and influences immune cell function. Because treatment of CF pulmonary exacerbation (CFPE) often improves body weight and lung function, we questioned whether serum IGF-1 trends were emblematic of these responses. Initially, we compared serum levels between healthy adults with CF and controls of similar age. We then measured serum IGF-1 throughout the CFPE cycle. We also investigated correlations among IGF-1 and other serum biomarkers during CFPE. Anthopometric, spirometric, and demographic data were collected. Serum IGF-1 concentrations were measured by ELISA. CF subjects in their usual state of health had lower serum IGF-1 levels than controls. Serum IGF-1 concentrations fell significantly from baseline at the beginning of CFPE. Treatment with intravenous antibiotics was associated with significant improvement in serum IGF-1 levels, body mass index (BMI), and percent-predicted forced expiratory volume in 1 sec (FEV1 %). At early and late CFPE, serum IGF-1 was directly correlated with FEV1 %, serum iron, hemoglobin concentration, and transferrin saturation (TSAT) and indirectly correlated with alpha-1-antitrypsin. This study not only supports the paradigm that CF is characterized by IGF-1 deficiency but also that trends in lung function, nutritional status, and serum IGF-1 are related. Improvements in all three parameters after antibiotics for CFPE likely highlight the connection between lung function and nutritional status in CF. Close correlations among IGF-1 and iron-related hematologic parameters suggest that IGF-1 may participate in CF iron homeostasis, another process that is known to be influenced by CFPE.

206 Clinical and paraclinical profile and risk of exacerbations in patients with cystic fibrosis attending a national reference center in Latin America

Cystic fibrosis (CF) is characterized by chronic airway and systemic inflammation complicated by intermittent episodes of acute exacerbations that contribute to significant morbidity. Objectives: To characterize and identify possible risk factors related to exacerbations in CF patients attending the National Reference Center in Uruguay. Methods: We analyzed data from all patients at the database of our center for the period 2011–2012. One patient who died and two patients, who underwent double lung transplantation, were excluded. Exacerbations were defined as acute/ sub-acute worsening of respiratory symptoms severe enough to warrant intravenous (IV) antibiotics and hospitalization. Results: 54 patients were included, 57.4% male, mean age 26±9, BMI 22±4. At least one of the most common mutation delta F508, was present in 35%, pancreatic insufficiency in 44%, diabetes in 9% and hemoptysis in 62%. Up to 70% were colonized with: Pseudomonas aeruginosa (PA) 52%, St. aureus 26.3%, Alcaligenes 13%, Stenotrophomonas 2.6%. Mean FVC 90.1±23%, mean FEV1 80.6±27.8; 18.5% FEV1 <60%. Patients received treatment with: inhaled tobramycin 44%, pulmozyme 51.8%, Hypertonic Saline solution 61%. 35% of patients had at least one exacerbation or hospitalization/year. Using a linear regression model no correlation was found between exacerbations and: sex, age, age at diagnosis, colonization with PA, or hemoptysis. Exacerbations were strongly associated with poor lung function (R: 0.51, p = 0.0001). Conclusions: Data from a well characterized CF population suggest that acknowledging trends in lung function may contribute to identify patients at risk of exacerbation and increased morbidity.

207 Non-invasive ventilation in cystic fibrosis

Cystic fibrosis (CF) is characterized by chronic airway and systemic inflammation complicated by intermittent episodes of acute exacerbations that contribute to significant morbidity. Objectives: To characterize and identify possible risk factors related to exacerbations in CF patients attending the National Reference Center in Uruguay. Methods: We analyzed data from all patients at the database of our center for the period 2011–2012. One patient who died and two patients, who underwent double lung transplantation, were excluded. Exacerbations were defined as acute/ sub-acute worsening of respiratory symptoms severe enough to warrant intravenous (IV) antibiotics and hospitalization. Results: 54 patients were included, 57.4% male, mean age 26±9, BMI 22±4. At least one of the most common mutation delta F508, was present in 35%, pancreatic insufficiency in 44%, diabetes in 9% and hemoptysis in 62%. Up to 70% were colonized with: Pseudomonas aeruginosa (PA) 52%, St. aureus 26.3%, Alcaligenes 13%, Stenotrophomonas 2.6%. Mean FVC 90.1±23%, mean FEV1 80.6±27.8; 18.5% FEV1 <60%. Patients received treatment with: inhaled tobramycin 44%, pulmozyme 51.8%, Hypertonic Saline solution 61%. 35% of patients had at least one exacerbation or hospitalization/year. Using a linear regression model no correlation was found between exacerbations and: sex, age, age at diagnosis, colonization with PA, or hemoptysis. Exacerbations were strongly associated with poor lung function (R: 0.51, p = 0.0001). Conclusions: Data from a well characterized CF population suggest that acknowledging trends in lung function may contribute to identify patients at risk of exacerbation and increased morbidity.

Secular trends in lung function and its relation to survival in Swedish 75 year olds 1976-2006

several studies have found that lung function correlates with survival in older people. We examined secular trends in lung function and its relation to survival in Swedish 75 year olds. representative samples from the general population in Gothenburg, Sweden, were examined at the age of 75 in 1976-77 (n = 743) and 2005-06 (n = 765) with comprehensive somatic and psychiatric examinations. Lung function was measured as peak expiratory flow (PEF). the mean PEF was higher in 75 year olds examined 2005-06 compared with those examined 1976-77 both among women (339 versus 307 l/min; P < 0.001) and men (490 versus 400 l/min, P < 0.001). The birth cohort effect was still significant after adjusting for a number of confounders. PEF correlated with survival between age 75 and 78 years among those examined in 1976-77 both in women (OR per 10 l/min increase in PEF = 1.112, 95% CI: 1.047-1.182) and in men (OR = 1.040, 95% CI: 1.015-1.066), but not in those examined 2005-06 (women: OR = 1.071, 95% CI: 0.965-1.188; men: OR = 1.000, 95% CI: 0.957-1.046). we found better lung function in the later-born cohort of 75 year olds, which was only partially explained by changes in smoking, height and weight, physical activity, socio-economic/educational factors and pulmonary/cardiovascular morbidity. The association between better lung function and short-term survival was strong in 1976-77, but had disappeared in 2005-06. More studies are needed to elucidate the role of lung function for long-term survival and identify other factors that explain the secular trends in lung function.

Idiopathic inflammatory myositis-associated interstitial lung disease: ethnicity differences and lung function trends in a British cohort

Interstitial lung disease (ILD) is an important feature of idiopathic inflammatory myositis (IIM). Factors associated with its development and progression remain incompletely understood. The authors report ethnicity differences and lung function trends that characterize the predilection for and natural history of ILD in a group of British patients with IIM. A 10-year retrospective analysis of patients with IIM at two hospitals was conducted. Demographic, clinico-radiological and laboratory features of cases with and without ILD were compared. Serial pulmonary function tests, including measurements of forced vital capacity, volume and diffusing capacity for carbon monoxide, were used to identify longitudinal patterns of lung disease. A total of 107 patients with IIM were identified. ILD was present in 37.4%, with non-specific interstitial pneumonia being the most common radiological pattern (75%). ILD was more common in IIM patients of Black ethnicity (OR 3.42), and in cases where ANA (OR 3.06) and anti-histidyl-tRNA synthetase (OR 3.2) antibodies were detected. In the ILD cohort, 50% deteriorated, defined as a drop in diffusing capacity of the lung for carbon monoxide by <15% or forced vital capacity <10% during the study period, occurring in all within a year of onset of ILD and significantly more frequently in those with a synchronous onset of IIM and ILD. Black ethnicity was not associated with poor lung function outcome. In IIM, the risk of developing ILD is significantly higher in patients of Black ethnicity. Progressive lung damage occurs in an appreciable subgroup of patients with IIM-ILD, heralded by functional lung decline at 1 year despite systemic immunomodulatory treatment.