Decline In FVC Research Articles

Pathologic expansion in the C9orf72 gene is associated with accelerated decline of respiratory function and decreased survival in amyotrophic lateral sclerosis

Introduction Respiratory insufficiency is the main cause of death in amyotrophic lateral sclerosis (ALS). As the C9orf72 repeat expansion represents the most common genetic risk factor for this disease, we studied whether C9orf72 modulates respiratory function and survival. Methods Demographic and clinical data, and C9orf72 status were collected from 372 ALS patients followed in our centre. Multiple regressions controlling for the C9orf72 expansion, diagnosis delay, region of onset, age, gender, and comorbid frontotemporal dementia were performed to evaluate the functional and respiratory status of the patients at baseline and during disease progression – assessed using the global ALSFRS-R score and its respiratory subscore, and the predicted forced vital capacity (%FVC). A Cox regression controlling for the same variables was carried out to analyse survival. Results At baseline, 32/372 (8.60%) patients carried the C9orf72 repeat expansion. We found that the C9orf72 mutation is an independent risk factor for a faster %FVC decline (p = .001) and shorter survival (p = .002). Conclusions In ALS patients with C9orf72 expansion, shorter survival probably derives from faster respiratory function decline. This finding may indicate a new pathogenic mechanism of C9orf72 in ALS.

Real-world retrospective observational study exploring the effectiveness and safety of antifibrotics in idiopathic pulmonary fibrosis

BackgroundPirfenidone and nintedanib are the only disease-modifying treatments available for idiopathic pulmonary fibrosis (IPF). Our aim was to test their effectiveness and safety in clinical practice.MethodsThis is a single-centre retrospective...

Monocyte Count as a Prognostic Biomarker in Patients with Idiopathic Pulmonary Fibrosis.

Rationale: There is an urgent need for simple, cost-effective prognostic biomarkers for idiopathic pulmonary fibrosis (IPF); biomarkers that show potential include monocyte count.Objectives: We used pooled data from pirfenidone and IFNγ-1b trials to explore the association between monocyte count and prognosis in patients with IPF.Methods: This retrospective pooled analysis included patients (active and placebo arms) from the following four phase III, randomized, placebo-controlled trials: ASCEND (NCT01366209), CAPACITY (NCT00287729 and NCT00287716), and INSPIRE (NCT00075998). Outcomes included IPF progression (≥10% absolute decline in FVC% predicted, ≥50 m decline in 6-minute-walk distance, or death), all-cause hospitalization, and all-cause mortality over 1 year. The relationship between monocyte count (defined as time-dependent) and outcomes was assessed using bivariate and multivariable models.Measurements and Main Results: This analysis included 2,067 patients stratified by monocyte count (at baseline: <0.60 × 109 cells/L [n = 1,609], 0.60 to <0.95 × 109 cells/L [n = 408], and ≥0.95 × 109 cells/L [n = 50]). In adjusted analyses, a higher proportion of patients with monocyte counts of 0.60 to <0.95 × 109 cells/L or ≥0.95 × 109 cells/L versus <0.60 × 109 cells/L experienced IPF progression (P = 0.016 and P = 0.002, respectively), all-cause hospitalization (P = 0.030 and P = 0.003, respectively), and all-cause mortality (P = 0.005 and P < 0.001, respectively) over 1 year. Change in monocyte count from baseline was not associated with any of the outcomes over 1 year and did not appear to be affected by study treatment.Conclusions: In patients with IPF, elevated monocyte count was associated with increased risks of IPF progression, hospitalization, and mortality. Monocyte count may provide a simple and inexpensive prognostic biomarker in IPF.

Respiratory impact of a grand tour: insight from professional cycling.

The aim of this study was to evaluate the respiratory function and symptom perception in professional cyclists completing a Grand Tour (GT). Nine male cyclists completed La Vuelta or Tour de France (2018/19). At study entry, airway inflammation was measured via fractional exhaled nitric oxide (FeNO). Respiratory symptoms and pulmonary function were assessed prior to the first stage (Pre-GT), at the second rest day (Mid-GT) and prior to the final stage of the GT (Late-GT). Sniff nasal inspiratory pressure (SNIP) was assessed at pre and late-GT timepoints. Seven cyclists reported respiratory symptoms during the race (with a prominence of upper airway issues). Symptom severity increased either mid or late-GT for most cyclists. A decline in FEV1 from pre-to-mid GT (-0.27 ± 0.24l, -5.7%) (P = 0.02) and pre-to-late GT (-0.27 ± 0.13l, -5.7%) (P < 0.001) was observed. Similarly, a decline in FVC (-0.22 ± 0.17l, -3.7%) (P = 0.01) and FEF25-75 (-0.49 ± 0.34l/s, -11%) (P = 0.02) was observed pre-to-late GT. Overall, eight (89%) and six (67%) demonstrated a clinically meaningful decline (> 200ml) in FEV1 and FVC during the GT follow-up, respectively. SNIP remained unchanged pre-to-late GT (n = 5), however, a positive correlation was observed between ΔSNIP and ΔFVC (r = 0.99, P = 0.002). GT competition is associated with a high prevalence of upper respiratory symptoms and a meaningful decline in lung function in professional cyclists. Further research is now required to understand the underpinning physiological mechanisms and determine the impact on overall respiratory health and elite cycling performance and recovery.

Post-COVID-19 pulmonary sequla: longterm follow up and management

Though it has been 8 months since the beginning of COVID-19 pandemic, number of cases and deaths are still seriously increasing. We still don't have enough evidence about the prognosis of patients who had COVID-19 pneumonia. In long term follow up we wonder if they will have rapid FVC decline, widespread fibrosis in computed tomography, loss in quality of life or increased mortality that we experience in idiopathic pulmonary fibrosis, chronic hypersensitivity pneumonia or autoimmune interstitial lung diseases. However, in elderly patients less severe dysfunction or non-progressive-fibrosis can cause morbidity and mortality. Therefore, if we consider millions of people who are affected by COVID-19, even a rare complication can cause serious health problem in social scale. Because of the importance of this issue randomized controlled trials should be rapidly planned on post-COVID fibrosis, COVID associated thrombosis, risk factors, prevention and treatment (1). In this review, the frequency, clinical importance, prevention and treatment of possible long-term sequels of COVID-19 pneumonia (pulmonary fibrosis, pulmonary embolism and pulmonary hypertension) will be discussed.

Respiratory decline in adult patients with Becker muscular dystrophy: A longitudinal study

Becker muscular dystrophy (BMD) is a rare hereditary neuromuscular disease, caused by a genetic defect in the Duchenne Muscular Dystrophy (DMD) gene. We studied the natural history of respiratory function and its affecting factors in 23 adult BMD patients. These important data are needed for (future) clinical trials in BMD but are largely lacking. Patients had a median age of 51 years (28–78y) and median follow-up duration of 14 years (2–25y). We analysed 190 pulmonary function measurements with a median interval of one year (1–17y) and measured a 1.00% decline of Forced Vital Capacity percent predicted (FVC%pred) per year (p = 0.004). Loss of ambulation significantly increased the annual rate of FVC decline and was dependent of patient's body mass index (BMI; p = 0.015), with increases in BMI correlating with an even more rapid deterioration of FVC. A decline in Medical Research Council (MRC) sum score was significantly correlated with a decline in FVC (p = 0.003). We conclude that adult BMD patients experience a significant but mild respiratory decline. However, this decline is significantly more rapid and clinically relevant after loss of ambulation, which warrants a more vigilant follow-up of respiratory function in this subgroup.

Serum markers of pulmonary epithelial damage in systemic sclerosis-associated interstitial lung disease and disease progression.

The course of systemic sclerosis-associated interstitial lung disease (SSc-ILD) is highly variable, and accurate prognostic markers are needed. KL-6 is a mucin-like glycoprotein (MUC1) expressed by type II pneumocytes, while CYFRA 21-1 is expressed by alveolar and bronchiolar epithelial cells. Both are released into the blood from cell injury. Serum KL-6 and CYFRA 21-1 levels were measured in a retrospective (n = 189) and a prospective (n = 118) cohort of SSc patients. Genotyping of MUC1 rs4072037 was performed. Linear mixed-effect models were used to evaluate the relationship with change in lung function parameters over time, while association with survival was evaluated with Cox proportional hazard analysis. In both cohorts, KL-6 and CYFRA 21-1 were highest in patients with lung involvement, and in patients with extensive rather than limited ILD. KL-6 was higher in patients carrying the MUC1 rs4072037 G allele in both cohorts. In patients with SSc-ILD, serum KL-6, but not CYFRA 21-1, was significantly associated with DLCO decline in both cohorts (P = 0.001 and P = 0.004, respectively), and with FVC decline in the retrospective cohort (P = 0.005), but not the prospective cohort. When combining the cohorts and subgrouping by severity (median CPI = 45.97), KL-6 remained predictive of decline in DLCO in both milder (P = 0.007) and more severe disease (P = 0.02) on multivariable analysis correcting for age, gender, ethnicity, smoking history and MUC1 allele carriage. Our results suggest serum KL-6 predicts decline in lung function in SSc, suggesting its clinical utility in risk stratification for progressive SSc-ILD.

A cluster-based analysis evaluating the impact of comorbidities in fibrotic interstitial lung disease

BackgroundComorbidities are frequent and have been associated with poor quality of life, increased hospitalizations, and mortality in patients with interstitial lung disease (ILD). However, it is unclear how comorbidities lead to these negative outcomes and whether they could influence ILD disease progression. The goal of this study was to identify clusters of patients based on similar comorbidity profiles and to determine whether these clusters were associated with rate of lung function decline and/or mortality.MethodsPatients with a major fibrotic ILD (idiopathic pulmonary fibrosis (IPF), fibrotic hypersensitivity pneumonitis, connective tissue disease-associated ILD, and unclassifiable ILD) from the CAnadian REgistry for Pulmonary Fibrosis (CARE-PF) were included. Hierarchical agglomerative clustering of comorbidities, age, sex, and smoking pack-years was conducted for each ILD subtype to identify combinations of these features that frequently occurred together in patients. The association between clusters and change in lung function over time was determined using linear mixed effects modeling, with adjustment for age, sex, and smoking pack-years. Kaplan Meier curves were used to assess differences in survival between the clusters.ResultsDiscrete clusters were identified within each fibrotic ILD. In IPF, males with obstructive sleep apnea (OSA) had more rapid decline in FVC %-predicted (− 11.9% per year [95% CI − 15.3, − 8.5]) compared to females without any comorbidities (− 8.1% per year [95% CI − 13.6, − 2.7]; p = 0.03). Females without comorbidities also had significantly longer survival compared to all other IPF clusters. There were no significant differences in rate of lung function decline or survival between clusters in the other fibrotic ILD subtypes.ConclusionsThe combination of male sex and OSA may portend worse outcomes in IPF. Further research is required to elucidate the interplay between sex and comorbidities in ILD, as well as the role of OSA in ILD disease progression.

Statins: cause of fibrosis or the opposite? Effect of cardiovascular drugs in idiopathic pulmonary fibrosis

Background and objectiveIdiopathic pulmonary fibrosis (IPF) is a progressive and irreversible interstitial lung disease with poor prognosis despite the recent availability of two antifibrotic drugs. Patients are more susceptible to cardiovascular comorbidities. In this study, we aimed to determine the impact of concomitant cardiovascular drugs on disease progression and survival in a modern IPF cohort. MethodsThe database of a tertiary referral centre for interstitial lung diseases in Belgium was reviewed for statin, antiaggregant, anticoagulant and metformin therapy. For a study period of four years, we noted both FVC% and DLCO% trajectories along with survival as outcome measurements. Results323 patients were included of which 45% had at least one cardiovascular comorbidity. 274 (86%) patients received antifibrotic therapy. Statin users (n = 171) displayed significantly slower annual FVC% (difference 2.9%, CI 1.6–4.4, p < 0.001) and DLCO% decline (difference 1.3%, CI 0.24–2.3, p = 0.013). Results for antiaggregant therapy (n = 152) were inconclusive: we found a trend for slower FVC decline (p = 0.098) and a numerically decrease in survival rates (HR 1.63, p = 0.074) in a multivariate Cox analysis. Anticoagulant use (n = 49) showed a trend towards worse DLCO decline (difference −1.3%, CI -2.6 - 0.02, p = 0.055).r Metformin (n = 28) therapy did not affect IPF progression in terms of pulmonary function test evolution or survival. ConclusionThis retrospective study demonstrated a benefit of statin therapy on IPF progression. Our observations emphasize the need for large clinical trials analysing the effect of statins, as well as other cardiovascular drugs, in the management of IPF patients.

Analysis of body mass index, weight loss and progression of idiopathic pulmonary fibrosis

BackgroundNintedanib is an approved therapy for idiopathic pulmonary fibrosis (IPF). Some patients treated with nintedanib experience weight loss. Exploratory data suggest that low body mass index or weight loss are associated with worse outcomes in patients with IPF. We investigated whether BMI at baseline or weight loss over 52 weeks was associated with FVC decline, or influenced the effect of nintedanib, in patients with IPF.MethodsUsing pooled data from the two INPULSIS trials, we analysed the rate of decline in FVC (mL/yr) over 52 weeks in patients treated with nintedanib and placebo in subgroups by baseline BMI (< 25; ≥25 to < 30; ≥30 kg/m2) and by weight loss over 52 weeks (≤5; > 5%) using random coefficient regression.ResultsIn the placebo group, the mean rate of FVC decline over 52 weeks was numerically greater in patients with lower baseline BMI (− 283.3 [SE 22.4], − 207.9 [20.9] and − 104.5 [21.4] in patients with BMI < 25 kg/m2, ≥25 to < 30 kg/m2 and ≥ 30 kg/m2, respectively). Nintedanib reduced the rate of FVC decline versus placebo in all subgroups by BMI, with a consistent treatment effect across subgroups (interaction p = 0.31). In the placebo group, the mean rate of FVC decline was numerically greater in patients with > 5% than ≤5% weight loss over 52 weeks (− 312.7 [SE 32.2] versus − 199.5 [SE 14.4] mL/year). Nintedanib reduced the rate of FVC decline versus placebo in both subgroups by weight loss, with a greater treatment effect in patients with > 5% weight loss (interaction p = 0.0008). The adverse event profile of nintedanib was similar across subgroups.ConclusionsIn patients with IPF, lower BMI and weight loss may be associated with faster decline in FVC. Nintedanib reduces the rate of FVC decline both in patients who lose weight on treatment and those who do not.Trial registrationClinicalTrials.gov; Nos. NCT01335464 and NCT01335477; URL: www.clinicaltrials.gov.

A study on pulmonary function tests among rice mill workers in Mysuru, Karnataka

Introduction and Aim: Rice is the largest consumed food grain in south India. Rice cultivation, harvesting and milling is done since ages in India. Respiratory diseases are greatly induced by the occupational dusts that are influenced by the duration of exposure. A large amount of dust is produced from rice milling process and hence the workers breathe air mixed with dust into their lungs every day. This study aims to assess the effect of rice mill dust on lung functions among rice mill workers.&#x0D; Materials and Methods: Fifty non-smoking male adult workers from rice mills were selected for the study and fifty age and sex matched from the general population who were not exposed to such occupational hazard were included as controls. Pulmonary function parameters (FVC, FEV1, FEV1/FVC, PEFR and MVV) were recorded using computerized RMS Helios Spirometer during their working hours in both the groups and were statistically analyzed by using student’s‘t’ test. Further the cases were classified according to the duration of exposure and inter group comparisons were made using one-way Anova.&#x0D; Results: Rice mill workers showed a significantly greater percentage of decline in FVC, FEV1, PEFR, MVV and also a significant decrease in FEV1/FVC ratio suggestive of obstructive pulmonary disorder. Also, there is a negative correlation between duration of exposure and deterioration of the lung function.&#x0D; Conclusion: The respiratory parameters were significantly declined among rice mill workers compared to controls.&#x0D;

Characteristics Associated with Accelerated Lung Function Decline in a Primary Care Population with Chronic Obstructive Pulmonary Disease.

BackgroundEstimates for lung function decline in chronic obstructive pulmonary disease (COPD) have differed by study setting and have not been described in a UK primary care population.PurposeTo describe rates of FEV1 and FVC decline in COPD and investigate characteristics associated with accelerated decline.Patients and MethodsCurrent/ex-smoking COPD patients (35 years+) who had at least 2 FEV1 or FVC measurements ≥6 months apart were included using Clinical Practice Research Datalink. Patients were followed up for a maximum of 13 years. Accelerated rate of lung function decline was defined as the fastest quartile of decline using mixed linear regression, and association with baseline characteristics was investigated using logistic regression.ResultsA total of 72,683 and 50,649 COPD patients had at least 2 FEV1 or FVC measurements, respectively. Median rates of FEV1 and FVC changes or decline were −18.1mL/year (IQR: −31.6 to −6.0) and −22.7mL/year (IQR: −39.9 to −6.7), respectively. Older age, high socioeconomic status, being underweight, high mMRC dyspnoea and frequent AECOPD or severe AECOPD were associated with an accelerated rate of FEV1 and FVC decline. Current smoking, mild airflow obstruction and inhaled corticosteroid treatment were additionally associated with accelerated FEV1 decline whilst women, sputum production and severe airflow obstruction were associated with accelerated FVC decline.ConclusionRate of FEV1 and FVC decline was similar and showed similar heterogeneity. Whilst FEV1 and FVC shared associations with baseline characteristics, a few differences highlighted the importance of both lung function measures in COPD progression. We identified important characteristics that should be monitored for disease progression.

The effect of statin therapy on disease-related outcomes in idiopathic pulmonary fibrosis: A systematic review and meta-analysis

BackgroundIdiopathic pulmonary fibrosis is a progressive disease and antifibrotic therapies do not reverse existing fibrosis. There has been emerging evidence of potential role for statins in idiopathic pulmonary fibrosis. The aim of this review is to synthesise the evidence on the efficacy of statins in idiopathic pulmonary fibrosis, focusing on associations with all-cause mortality, disease-specific mortality and change in pulmonary function. MethodsMedline and Embase were reviewed to identify relevant publications. Studies were selected if they examined disease-related outcomes including mortality, pulmonary function and adverse events in people with idiopathic pulmonary fibrosis receiving statin therapy. ResultsFive studies with a total of 3407 people with IPF were selected and analysed. The overall risk of bias of five included studies was moderate to serious. In the fixed effect meta-analysis, statin use was associated with a reduction in mortality (RR 0.8; 95% CI 0.72–0.99). However, in the random effects model, there was no longer any significant association between statin use and all-cause mortality (RR 0.87; 95% CI 0.68–1.12). There was no statistically significant association between statin use and decline in FVC % predicted. ConclusionThere is currently insufficient evidence to conclude the effect of statin therapy on disease-related outcomes in idiopathic pulmonary fibrosis. Considering the limitations of available literature, we would recommend a prospective cohort study with capture of dosage and preparation of statin, statin adherence and use of concurrent antifibrotic treatment. PROSPERO registration numberCRD42019122745.

EFFECT OF NINTEDANIB IN PATIENTS WITH PROGRESSIVE FIBROSING ILDS AND PRESERVED LUNG FUNCTION AT BASELINE: FURTHER ANALYSES OF THE INBUILD TRIAL

EFFECT OF NINTEDANIB IN PATIENTS WITH PROGRESSIVE FIBROSING ILDS AND PRESERVED LUNG FUNCTION AT BASELINE: FURTHER ANALYSES OF THE INBUILD TRIAL

CLINICAL MODIFIERS TO IMMUNOSUPPRESSION RESPONSE IN FIBROTIC HYPERSENSITIVITY PNEUMONITIS

SESSION TITLE: Occupational and Environmental Lung Disease SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: Patients with hypersensitivity pneumonitis (HP) are often treated with immunosuppression (IS) with varied response. Nintedanib, an antifibrotic medication, is effective in progressive fibrotic interstitial lung diseases, including HP (Flaherty, et al, 2019). Given the option of treating with IS or nintedanib, it is unclear which patients should be preferentially treated with IS. We aimed to identify IS treatment effect modifier variables in patients with fibrotic HP. METHODS: This was a single center retrospective study of HP patients from 1/2004-1/2018. Patients were excluded for < 6-month follow up, exposure to IS at initial evaluation, or no fibrosis on high-resolution CT (HRCT). Patients exposed to IS (prednisone, azathioprine, or mycophenolate) were compared to those without exposure (control). To account for baseline differences between treatment groups, propensity score matching was performed; covariates included age, gender, ethnicity, smoking history, baseline forced vital capacity (FVC%), diffusion of lung for carbon monoxide (DLCO%). Potential treatment effect modifier variables were abstracted from the medical record. Transplant-free survival was assessed using multivariable Cox proportional hazards model that included an interaction term for each potential modifier and IS exposure (modifier variable x treatment); p-interaction <0.05 was considered significant for treatment effect modifier. FVC% change over 1-year from IS initiation was estimated using linear mixed-effect model with an interaction term for each potential modifier and IS exposure included as fixed effects. RESULTS: After propensity matching, there were 92 patients included (46 in the IS and 46 in the non-IS groups); there were no baseline differences (p>0.05 for all variables). None of the patient demographics, baseline lung function, peripheral blood counts, blood inflammatory markers, serologies, and HRCT features modified treatment effect of IS on transplant-free survival (p-interaction >0.05 for all variables). In patients exposed to IS, BAL lymphocyte >20% was associated with improved FVC% at 1 year (+7.5% vs -2.8, p=0.044), while traction bronchiectasis on HRCT (-4.0% vs + 7.2%, p=0.007) and usual interstitial pneumonia pattern on HRCT or pathology (-9.1% vs +1.6%, p=0.022) was associated with decline in FVC% at 1 year. CONCLUSIONS: In fibrotic HP patients, the association between IS treatment and transplant-free survival did not differ by commonly assessed baseline characteristics. However, “IPF-like features” were associated with faster FVC% decline, while “inflammatory” markers like BAL lymphocytosis was associated with improved FVC% in fibrotic HP patients exposed to IS. CLINICAL IMPLICATIONS: This study identified treatment effect modifiers to immunosuppressive therapy which may help guide treatment decisions in patients with fibrotic hypersensitivity pneumonitis. DISCLOSURES: No relevant relationships by Traci Adams, source=Web Response No relevant relationships by KIRAN BATRA, source=Web Response No relevant relationships by ESTHER DE BOER, source=Web Response No relevant relationships by Craig Glazer, source=Web Response No relevant relationships by Margaret Kypreos, source=Web Response No relevant relationships by Chad Newton, source=Web Response

PLEUROPARENCHYMAL FIBROELASTOSIS FROM BEGINNING TO END: FOLLOWING THE DISEASE COURSE OF THIS RARE INTERSTIAL LUNG DISEASE

SESSION TITLE: Medical Student/Resident Diffuse Lung Disease SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Pleuroparenchymal fibroelastosis has become more recognized in the clinical literature as an entity characterized by predominantly upper lobe localization of pleural and subpleural fibrosis and elastosis. In this case report, we present a patient with idiopathic PPFE throughout the course of several hospital admissions over a two-year time period: from her initial presentation to her eventual compassionate extubation. CASE PRESENTATION: A 63 y/o Hispanic female presented with dyspnea secondary to a L pneumothorax. A thorough rheumatologic and infectious work-up was performed (Table 1). A HRCT demonstrated "tree-in bud pathology, bronchiectasis, and changes not consistent w/ UIP or NSIP.” She completed a 6-minute walk test on room air upon initial presentation, but 10 months later she developed another large pneumothorax over her LUL. She was again admitted one month later for a R pneumothorax requiring chest tube decompression. It was during this prolonged admission that a CT thorax demonstrated worsening fibrotic lung disease with pleural thickening and architectural distortion (Image 1, Image 2). Another 6-minute walk test demonstrated desaturation to 88% on room air with 1L O2 requirement upon exertion. By her 6th hospitalization, a 6-minute walk test demonstrated significant respiratory distress with exertion, despite supplemental O2. 2 years following her initial presentation, the patient was admitted for hypoxic respiratory failure, intubated in the ED and ultimately compassionately extubated. DISCUSSION: The gold-standard for diagnosis is histopathologic confirmation. This patient was referred for a lung biopsy several times, but these records could not be confirmed. Instead, at a multidisciplinary conference with Rheumatology, Pulmonology, ID, and Radiology, the patient's clinical course and imaging were reviewed and found to be most consistent with PPFE. The reported mean age of presentation of PPFE is 49, while our patient presented later in life with severe radiologic features, suggesting years of subclinical progression. Some studies have suggested that the decline of FVC in patients can be separated into two heterogeneous groups – one with decline in FVC over years and those that rapidly deteriorate. Given our patient's rapid progression over two years; she likely falls into the latter group. Her course fits with prior studies indicating a subset of patients with progressive disease may have a median survival of <5 years. CONCLUSIONS: This is a singular case report of an elderly female patient, whose disease course was captured in the advanced stage of disease. The patient was referred for transplant, but due to her functional status and low BMI, she was not deemed an appropriate candidate. Despite more recognition of this condition, further longitudinal evaluation of patients is required in order to determine the nature of the course of disease. Reference #1: Chua F, Desai SR, Nicholson AG, et al. Pleuroparenchymal fibroelastosis a review of clinical, radiological, and pathological characteristics. Ann Am Thorac Soc. 2019;16(11):1351-1359. https://doi.org/10.1513/AnnalsATS.201902-181CME Reference #2: Yoshida Y, Nagata N, Tsuruta N, et al. Heterogeneous clinical features in patients with pulmonary fibrosis showing histology of pleuroparenchymal fibroelastosis. 2015. https://doi.org/10.1016/j.resinv.2015.11.002 Reference #3: Tanizawa K, Handa T, Kubo T, et al. Clinical significance of radiological pleuroparenchymal fibroelastosis pattern in interstitial lung disease patients registered for lung transplantation: A retrospective cohort study. Respir Res. 2018;19(1). https://doi.org/10.1186/s12931-018-0860-6 DISCLOSURES: No relevant relationships by Rodrigo Garcia Tome, source=Web Response No relevant relationships by Chongiin Kim, source=Web Response

UNCARBOXYLATED MATRIX G1A PROTEIN AS A PREDICTOR OF LUNG FUNCTION

SESSION TITLE: Updates in Diffuse and Orphan Lung Diseases SESSION TYPE: Original Investigations PRESENTED ON: October 18-21, 2020 PURPOSE: Matrix G1a protein (MGP) is expressed in elastin rich tissue and is a potent inhibitor of calcification and subsequently of elastin degradation. MGP is activated by vitamin K-dependent mechanisms from uncarboxylated MGP (ucMGP) to carboxylated MGP. Prior studies have demonstrated lower vitamin K levels are associated with higher elastin degradation in COPD and idiopathic pulmonary fibrosis, suggesting that the MGP pathway may be important in maintaining lung function. Whether circulating levels of ucMGP are associated with lung function and chronic lung disease remains unclear. METHODS: We examined participants of the Framingham Heart Study who underwent measurement of plasma ucMGP levels and lung function testing (% predicted FEV1, FVC, FEV1/FVC, TLC and DLCO). Participants with past myocardial infarction, heart failure or end stage renal disease were excluded. We used multivariable linear and logistic regression to examine the association of ucMGP with lung function and the presence of restrictive lung disease (defined as % predicted FVC<80% and FEV1/FVC>70%) and obstructive lung disease (defined as FEV1/FVC<70% and % predicted FEV1<80%). Analyses were adjusted for age and sex, and additionally for height, BMI and smoking history. RESULTS: A total of 6160 participants were included, with mean age of 48 and 54% women. Higher ucMGP levels were associated with lower FEV1 (multivariable-adjusted β -0.007, s.e. 0.002, p<0.0001), FVC (β-0.007 s.e. 0.002, p<0.0001) and TLC (β-0.016 , s.e. 0.025, p=0.52). By contrast, ucMGP levels were not associated with FEV1/FVC ratio (p=0.17) or DLCO (p=0.25). In multivariable-adjusted analyses, participants in the highest ucMGP quartile had a 1.4% lower percent predicted FEV1 (p=0.01) and percent predicted FVC (p=0.006). Participants in the highest quartile of ucMGP had a 2-fold greater odds of having restrictive lung disease in age- and sex-adjusted analyses (OR 2.13, 95% CI 1.37-3.30, p=0.0002) compared with individuals in the lowest ucMGP quartile. This association was attenuated upon multivariable adjustment. We found no association with obstructive lung disease. CONCLUSIONS: Higher levels of ucMGP were associated with lower FEV1, FVC, and the presence of restrictive lung disease, while no association is observed with the FEV1/FVC ratio. This suggests that the MGP pathway may play a role in restrictive lung disease, even among largely asymptomatic adults in the community. CLINICAL IMPLICATIONS: Higher levels of ucMGP were associated with lower FEV1 and FVC as well as a greater odds of restrictive lung disease. Whether targeting the MGP pathway with interventions such as vitamin K supplementation may reduce the decline of FEV1 and FVC needs to further be investigated. DISCLOSURES: No relevant relationships by Paul Courchesne, source=Web Response One time consultant relationship with Merck Research Laboratory Please note: $1001 - $5000 Added 04/07/2020 by Josee Dupuis, source=Web Response, value=Honoraria Removed 04/07/2020 by Josee Dupuis, source=Web Response One time consultant relationship with Merck Research Laboratories Please note: $1001 - $5000 Added 04/07/2020 by Josee Dupuis, source=Web Response, value=Honoraria No relevant relationships by Jennifer Ho, source=Web Response no disclosure on file for Shih-Jen Hwang; No relevant relationships by martin larson, source=Web Response No relevant relationships by Dong Heon Lee, source=Web Response no disclosure on file for Daniel Levy; no disclosure on file for Jianto Ma; No relevant relationships by Jenna McNeill, source=Web Response no disclosure on file for George O'Connor; No relevant relationships by Samantha Paniagua, source=Web Response no disclosure on file for CHEN YAO

AUTOPHAGIC MYOPATHIES / MYOFIBRILLAR MYOPATHIES / DISTAL MYOPATHIES / POMPE DISEASE: P.06 Long-term effects of enzyme replacement therapy in an elderly cohort of late-onset Pompe disease patients

First longitudinal studies showed that enzyme replacement therapy (ERT) effects in late-onset Pompe disease (LOPD) seem to peak at 2-3 y often followed by a secondary decline. We aimed to examine long-term ERT effects in an elderly cohort of LOPD. Main inclusion criteria were age at diagnosis and onset of ERT > 50 y and ERT duration > 7 y. Outcome parameters included MRC sum-score (% of max.), 6-minute walk test 6MWT (% predicted), Quick Motor Function Test QMFT (% of max.), forced vital capacity FVC sitting and supine (% predicted), CK levels, and IgG antibody titers against alglucidase alfa. Six patients (3 f/3 m) qualified for the study, all were ambulatory at time of diagnosis. The median age at onset was 49 y (range 40-64), age at diagnosis and start of ERT 63 y (52-69), and age at last outcome 72.5 y (59-80). The median ERT duration was 8 y (7-12). Two patients became wheelchair-dependent. Two females were still able to walk unassisted and did not need noninvasive ventilation at the end of follow-up. There was no association between clinical outcome and genetic data, skeletal muscle histology, residual enzyme activity, and antibody titers. Peak antibody titers ranged from 0 to high with highest titers in best responders. Patients with lower ERT dosages had higher antibody titers. At least 50% of patients initially benefited from ERT. All patients showed a decline in FVC sitting during long-term follow-up, whereas 33% had a stabilization or improvement of FVC supine. 33% showed a stabilization or improvement of muscle strength. In contrast, QMFT deteriorated in 83% over time. However, 6MWT improved in 67% during a median ERT period of 8 y. CK levels continuously decreased in all patients. Best long-term results were seen in 6MWT, FVC supine and MRC sum-scores. Better ERT effects on FVC supine vs. sitting might hint to a preferential long-term effect on diaphragm muscles. In conclusion, ERT effects were heterogeneous but in general beneficial in elderly LOPD patients.

Cause of mortality and sarcopenia in patients with idiopathic pulmonary fibrosis receiving antifibrotic therapy.

Recent research has highlighted the fundamental role of sarcopenia, characterized by loss of skeletal muscle mass and strength, with a risk of poor outcomes. AFT preserves lung function by preventing the annual decline in FVC and is associated with improved outcomes in patients with IPF. However, altered cause of death and prognostic implications of sarcopenia in patients with IPF receiving AFT remain unknown. This study comprised two cohorts of patients with IPF receiving AFT, historical cohort of IPF patients without AFT and controls. The cause of mortality was compared with a historical cohort. Sarcopenia was assessed by measuring the ESMCSA and ESMMA via CT. Patients with IPF had smaller ESMCSA and lower ESMMA but similar BMI than controls, suggesting patients with IPF had skeletal muscle loss without any obvious body weight loss. The most common cause of mortality in patients receiving AFT was chronic respiratory failure, accounting for approximately 60%, and decreased proportions of LC were found. Subsequently, low ESMCSA was an independent prognostic factor associated with worse survival rates. Furthermore, combined assessment of ESMCSA , %FVC predicted and BMI values provided clear prognostic distinction. Patients with IPF receiving AFT showed skeletal muscle loss without obvious weight loss. These patients mostly died by chronic respiratory failure, and skeletal muscle wasting has prognostic significance, suggesting that preventing sarcopenia as well as preserving lung function are important for managing these patients.

Mediastinal lymph node enlargement in idiopathic pulmonary fibrosis: relationships with disease progression and pulmonary function trends

Background and objectivesEvidence of mediastinal Lymph Node Enlargement (LNE) on CT scan is a common finding in idiopathic pulmonary fibrosis (IPF). We sought to investigate whether the involvement of mediastinal lymph nodes is associated with accelerated disease progression, and explored the changes occurring in mediastinal lymph nodes during the radiological follow up of these patients.MethodsThis retrospective study included IPF patients referred to a single ILD centre in Italy. A consensus-based assessment of mediastinal LNE on chest CT scan was performed by two thoracic radiologists. Kaplan-Meier curves and multivariate Cox proportional hazards regression were used to assess hazard ratios for mortality and disease progression (defined as categorical FVC decline ≥10%). The annualized rates of change in functional parameters for each patient were calculated using mixed linear models.ResultsThe study population consisted of 152 IPF patients, of whom 135 (89%) received antifibrotic treatment for IPF during the study follow up. Patients having evidence of 3 or more enlarged mediastinal lymph nodes on baseline CT scan showed increased rates of mortality (HR 5.03, 95% CI 1.86–13.62, p ≤ 0.001) and significant disease progression (HR 2.99, 95% CI 1.22–7.33, p = 0.17) as compared to patients without LNE, after adjusting for GAP stage. Among 62 patients with LNE who underwent a follow up CT scan of the chest and received antifibrotic treatment, 57 (92%) maintained evidence mediastinal LNE over time.ConclusionsDiffuse mediastinal lymph node involvement predicts clinically meaningful functional deterioration in patients with IPF.