Decline In Pulmonary Function Research Articles

Progression of Pulmonary Function and Correlation with Survival Following Stereotactic Body Radiotherapy of Central and Ultracentral Lung Tumors.

Simple SummaryStereotactic body radiotherapy (SBRT) enables highly focused irradiation of lung tumors and has become a standard treatment. However, SBRT of lung tumors with close proximity to the central airways or mediastinum (central and ultracentral tumors) is associated with an increased risk for severe complications (bronchial bleeding, blockage of bronchi with loss of lung function). This retrospective study analyzed lung function and survival after risk-adapted approaches of SBRT in 107 central and ultracentral lung tumors. Lung function (vital capacity, forced expiratory volume in the first second) showed a statistically significant but in absolute numbers modest decrease that correlated moderately with the maximum radiation dose to the central airways. Stronger decrease in pulmonary function was found to be associated with limited survival. Consequently, lung function tests should be an integral element of follow-up after SBRT of lung tumors with proximity to the central airways or mediastinum.Stereotactic body radiotherapy (SBRT) to central and ultracentral lung tumors carries a risk of excessive toxicity. This study analyzed changes in pulmonary function tests (PFT) and their correlation with overall survival (OS) in 107 patients following central (n = 62) or ultracentral (n = 45) lung SBRT. Ultracentral location was defined as planning target volume overlap with the proximal bronchial tree (PBT). Vital capacity (VC) (−0.3 l, absolute −9.4% of predicted, both p < 0.001) and forced expiratory volume in the first second (FEV1s) (−0.2 l, absolute −7.7% of predicted, both p < 0.001) significantly decreased following SBRT. Higher maximum dose to the PBT significantly correlated with a steeper decline in VC (p = 0.005) and FEV1s (p = 0.03) over time. Pronounced decline in FEV1s between 6 and 12 months (HR = 0.90, p = 0.006) and pronounced decline in VC between baseline and 12 months (HR = 0.95, p = 0.004) independently correlated with worse OS. Consequently, PFT presented a statistically significant albeit clinically mild decrease in lung volumes following central and ultracentral SBRT that correlated moderately with maximum dose to the PBT. Stronger decline in pulmonary function was associated with constrained survival, advocating consequent performance of PFT during follow-up.

A RARE TWIST: LYMPHANGIOLEIOMYOMATOSIS PLUS DIFFUSE LARGE B-CELL LYMPHOMA

SESSION TITLE: Medical Student/Resident Diffuse Lung Disease SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Lymphangioleiomyomatosis (LAM) is a rare systemic disease resulting in cystic lung destruction, recurrent pneumothoraces, chylous pleural effusions, and abdominal tumors. This multisystem disease most commonly affects women of childbearing age, resulting in stepwise decline in pulmonary function, with clinically apparent hypoxemia developing in most patients within a decade after onset of symptoms. Here we present a rare case of late-onset LAM with concurrent high grade B-cell lymphoma. CASE PRESENTATION: The patient is a 62-year-old female nonsmoker with a remote history of spontaneous pneumothorax who presented due to pleuritic chest pain at rest. Chest CT revealed innumerable pulmonary cysts up to 15 mm, few solid noncalcified pulmonary nodules, multiple complex mediastinal lesions, and a 30% left anterior pneumothorax. Chest tube was placed; the patient was admitted. A nontender swelling was noted on the skull which the patient attributed to a work injury several months prior. MRI showed a 5 cm lytic lesion involving the left frontal bone and subgaleal space with hypercellular diffusion pattern. Craniectomy with resection was performed; pathology revealed high-grade B cell lymphoma. CT abdomen revealed a 4x4 cm right-sided irregular exophytic renal mass. The patient had VEGF-D level of 1382 pg/mL, which, combined with diffuse cystic lung disease, was consistent with a diagnosis of LAM. The patient was discharged and underwent chemotherapy and radiation in the outpatient setting. Two months later, she was readmitted with recurrent left pneumothorax. She failed doxycycline chemical pleurodesis (as there was a nation-wide talc shortage) and went for VATS decortication, pleurectomy, LLL wedge resection, and mechanical pleurodesis. Immunohistochemistry studies on lung pathology confirmed LAM (Table 1). DISCUSSION: LAM may develop sporadically, or may arise in a patient with preexisting tuberous sclerosis complex. The clinical presentation varies and may include cough, dyspnea, recurrent pneumothorax, pleural effusion, or respiratory failure. Overall, the patient’s family history and clinical presentation was not consistent with tuberous sclerosis complex. This is a case of likely sporadic LAM in a patient with recurrent pneumothorax, the first being 5 years prior to this presentation. The concurrent diffuse large B cell lymphoma of the skull adds an interesting twist, as there have only been case reports of LAM occurring with malignant lymphoma. CONCLUSIONS: Although LAM is diagnosed at a median age of 35, more women are being diagnosed at an older age. Pleurodesis after the first occurrence of pneumothorax should be considered due to the high rate of recurrence, as seen in this patient who had multiple pneumothoraces and failed chemical pleurodesis. Sirolimus is also recommended for LAM but this patient’s concurrent treatment for lymphoma complicates her treatment options. Reference #1: McCormack FX, Gupta N, Finlay GR, et al. Official American Thoracic Society/Japanese Respiratory Society Clinical Practice Guidelines: Lymphangioleiomyomatosis Diagnosis and Management. Am J Respir Crit Care Med. 2016;194(6):748-761. doi:10.1164/rccm.201607-1384ST Reference #2: Park S, Lee EJ. Diagnosis and treatment of cystic lung disease. Korean J Intern Med. 2017 Mar;32(2):229-238. doi: 10.3904/kjim.2016.242. Epub 2017 Feb 28. Reference #3: Jawad H, Walker CM, Wu CC, Chung JH. Cystic interstitial lung diseases: recognizing the common and uncommon entities. Curr Probl Diagn Radiol. 2014 May-Jun;43(3):115-27. doi: 10.1067/j.cpradiol.2014.01.001. DISCLOSURES: No relevant relationships by Helen Li Mitchell, source=Web Response No relevant relationships by Sushant Soni, source=Web Response No relevant relationships by Justin Thomas, source=Web Response No relevant relationships by Shawnt Tosonian, source=Web Response

Association of Anti–Topoisomerase I Antibodies of the IgM Isotype With Disease Progression in Anti–Topoisomerase I–Positive Systemic Sclerosis

ObjectiveAnti–topoisomerase I (anti–topo I) autoantibodies in systemic sclerosis (SSc) are associated with diffuse skin involvement and interstitial lung fibrosis. Thus far, however, the relationship between anti–topo I antibody response and disease course has not yet been fully evaluated. This study was undertaken to gain insight into the association between characteristics of the anti–topo I antibody response and clinical disease course in SSc patients positive for anti–topo I antibodies.MethodsLevels of anti–topo I IgG, anti–topo I IgM, and anti–topo I IgA were assessed in consecutive serum samples obtained from patients at baseline who were positive for anti–topo I IgG in the Leiden Combined Care In Systemic Sclerosis (CCISS) cohort. One‐year disease progression was defined by a relevant increase in modified Rodnan skin thickness score (MRSS), decline in pulmonary function, development of digital ulcers, renal crisis, and pulmonary hypertension, and/or mortality. Validation was performed in SSc patients who were positive for anti–topo I from the Oslo University Hospital and University Hospital Zurich.ResultsOf the 103 patients with anti–topo I IgG in the CCISS cohort, clinical data were available to assess 1‐year disease progression in 81 patients. Of these 81 patients, 23 (28%) had disease progression. At baseline, patients with disease progression were significantly more often anti–topo I IgM–positive than those who did not experience disease progression (21 [91%] of 23 versus 33 [57%] of 58; P < 0.01). This finding was confirmed in the independent validation samples.ConclusionIn SSc patients who were anti–topo I IgG–positive, presence of anti–topo I IgM, which might be considered as a surrogate for an ongoing autoreactive B cell immune response, is associated with disease progression.

DMD – THERAPY: P.292 Ataluren delays loss of ambulation and decline in pulmonary function in patients with nonsense mutation Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is a fatal, rare, X-linked disease characterized by progressive muscle weakness. Approximately 10–15% of DMD cases are caused by a nonsense mutation (nmDMD) in the dystrophin gene, resulting in the absence of functional dystrophin. Ataluren (10, 10, 20 mg/kg [morning, midday, and evening]) targets the underlying cause of nmDMD, enabling the formation of full-length, dystrophin. Study 019 was a phase 3, long-term safety study that enrolled nmDMD patients from prior ataluren clinical trials (NCT01557400) (N=94).

DMD – THERAPY: P.294 Does steroid therapy influence pulmonary function decline in adults with Duchenne muscular dystrophy after loss of ambulation?

Data from longitudinal paediatric Duchenne Muscular Dystrophy (DMD) cohorts has shown significant benefits of corticosteroids (CS) in patient treatment and management. Additionally, current scientific literature suggests that CS therapy delays the onset of pulmonary decline by approximately two years. However, there is limited data on the effects of CS in patients after loss of ambulation. Despite the updated in 2018 standards of care for DMD, there is still inconsistency in clinical care for non-ambulant patients across the UK.

Clinical presentation and prognostic analysis of adult patients with Langerhans cell histiocytosis with pulmonary involvement

BackgroundThe study aimed to investigate the clinical features and prognosis factors of adult patients with Langerhans cell histiocytosis (LCH) with pulmonary involvement, especially multisystem (MS) LCH with pulmonary involvement.MethodsWe retrospectively analyzed the demographic materials, clinical features and treatment outcomes of 119 adult LCH patients with pulmonary involvement at our center from January 1990 to November 2019.ResultsAmong 119 patients, 13 (10.9%) had single-system (SS) LCH, and 106 (89.1%) had MS-LCH with pulmonary involvement. SS-LCH patients had higher smoking rate (84.6% vs 52.8%, P = 0.026) and smoking index (300 vs 200, P = 0.019) than MS-LCH patients. The percentage of respiratory symptoms of SS-LCH patients was higher than MS-LCH patients (84.6% vs 53.8%, P = 0.034). Pulmonary function was impaired in 83.8% of the patients, and DLCO was the parameter most frequently impaired, accounting for 81.1%. The median DLCO was 65.1% predicted. Patients with pneumothorax had significantly worse DLCO (P = 0.022), FEV1 (P = 0.000) and FEV1/FVC (P = 0.000) than those without pneumothorax. During the follow-up, 72.4% of the patients had stable pulmonary function, and 13.8% showed improvements after chemotherapy. The estimated 3-year OS and EFS were 89.7 and 58.3%, respectively. Patients with a baseline FEV1 ≤ 55% predicted had worse OS. A history of pneumothorax indicated worse EFS and cytarabine based therapy predicted better EFS.ConclusionsAn FEV1 ≤ 55% predicted and a history of pneumothorax at diagnosis indicated a poor prognosis. Cytarabine based regimen may arrest the decline in pulmonary function in LCH patients with pulmonary involvement and improve EFS.

&lt;em&gt;Helicobacter&amp;nbsp;pylori&lt;/em&gt; is associated with weakened pulmonary function and reduced incidence of allergic conditions in patients with chronic cough

The present study aimed to investigate the potential association between Helicobacter pylori (a H. pylori) positive state and chronic cough. A clinical observational study with systematic analysis was performed, including 278 patients with complaints of chronic cough and 148 healthy controls. a H. pylori positive state was present in 61.2% of the patients in the chronic cough group and 68.9% in the chronic refractory cough group, as opposed to 43.9% in the control group. There was a significant improvement in 65.5% of the patients with chronic refractory cough following successful a H. pylori eradication therapy. In addition, patients with chronic cough exposed to a H. pylori exhibited decreased pulmonary function with a decrease in forced expiratory volume in 1 sec by 84 ml, a decrease in the forced vital capacity by 53 ml and a decrease in maximal vital capacity by 46 ml. The difference was even more obvious in the chronic refractory cough group. The allergy status differed significantly according to age between a H. pylori-positive and -negative cases in the cough variant asthma and allergic cough groups. Among patients aged <40 years, a H. pylori-positive cases had a lower prevalence of atopy and lower total serum immunoglobin E levels compared with a H. pylori-negative cases. However, there was no significant association between a H. pylori status and C-reactive protein levels, erythrocyte sedimentation rate or eosinophil count in the peripheral blood. In conclusion, the present study demonstrated that a H. pylori infection may be a factor associated with chronic cough and it may be associated with a decline in pulmonary function and reduced incidence of allergic conditions. Thus, a H. pylori may represent a target for the treatment of chronic cough.

SARS-CoV-2 infection of human ACE2-transgenic mice causes severe lung inflammation and impaired function.

Although animal models have been evaluated for Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection, none have fully recapitulated the severe lung disease phenotypes seen in hospitalized human cases. Here, we evaluate transgenic mice expressing the human ACE2 receptor driven by the cytokeratin-18 gene promoter (K18-hACE2) as a model of SARS-CoV-2 infection. Intranasal inoculation of SARS-CoV-2 in K18-hACE2 mice results in high levels of viral infection in lungs with spread to other organs. A decline in pulmonary function occurs 4 days after peak viral titer and correlates with infiltration of monocytes, neutrophils, and activated T cells. SARS-CoV-2-infected lung tissues show a massively upregulated innate immune response with signatures of NF-kB-dependent, type I and II interferon signaling, and leukocyte activation pathways. Thus, the K18-hACE2 model of SARS-CoV-2 infection shares many features of severe COVID-19 infection and can be used to define the basis of lung disease and test immune and antiviral-based countermeasures.

The prognostic value of fixed time and self-paced walking tests in patients diagnosed with idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic fibrosing interstitial pneumonia that has an unknown etiology. The natural history of the disease is characterized by a progressive decline in pulmonary function and overall health and well-being. The median survival time is between 2-3 years; however, the disease course is variable and unpredictable. The twelve-minute walking test (12MWT) and six-minute walking test (6MWT) are two fixed time tests that are commonly used in clinical practice. Our short and clinically oriented narrative review attempted to summarize current evidence supporting the use of fixed time, self-paced walking tests in predicting the outcome of patients diagnosed with IPF. A number of studies have justified that the 6MWT is a simple, cost-effective, well documented, fixed time, and self-paced walking test which is a valid and reliable measure of disease status and can also be used as a prognostic tool in patients with IPF. However, there is a need for dedicated and validated reference equations for this population of patients. It is also necessary to fill the knowledge gap about the role of the 12MWT. We hypothesize that it would be useful in evaluating patients that are in the early stages of the disease.

The Role of Enhanced Recovery Programmes in Elderly Patients Undergoing Thoracic Surgery

An ageing population and increasing use of imaging techniques have resulted in a greater number of elderly patients being diagnosed with localised, early stage non-small cell lung cancer (NSCLC). Several physiologic factors contribute to the challenge of thoracic surgery in elderly patients: age-related decline in pulmonary function, comorbid disease such as ischaemic heart disease, diabetes and osteoporosis; and advanced COPD in lifelong smokers. This article will discuss the potential advantages of enrolling elderly patients undergoing thoracic surgery on an enhanced recovery after surgery programme and the effect of such programmes on patient outcomes. Several interventions implemented in the pre-, intra- and post-op periods have been shown to reduce morbidity and mortality in elderly patients undergoing pulmonary resection. No single intervention has the capacity to reduce morbidity and mortality in the elderly undergoing pulmonary resection; however, a series of interventions implemented as an ERAS programme has the potential to improved outcomes in this patient population.

Relationship between pulmonary function and albuminuria in type 2 diabetic patients with preserved renal function

BackgroundAlbuminuria is the early manifestation of the pathogenesis of diabetic nephropathy (DN). The current study was to investigate the relationship of pulmonary function with albuminuria in type 2 diabetic patients with preserved renal function to evaluate the role of pulmonary function in the early stage of DN.MethodsA total of 326 patients with type 2 diabetes mellitus (T2DM) including 270 without albuminuria and 56 with albuminuria, and 265 non-diabetic patients were enrolled. The patients’ general information, and the parameters of pulmonary function, including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC, total lung capacity (TLC), diffusion capacity for carbon monoxide of lung (DLCO) were compared between T2DM and control groups, as well as T2DM patients with and without albuminuria groups. All pulmonary function parameters were expressed as a percentage of those predicted (%pred). Logistic regression models were constructed to test the association of albuminuria and pulmonary function.ResultsThe values of FVC%pred, FEV1%pred, TLC%pred and DLCO%pred were lower, and the proportion of subjects with FVC%pred < 80, FEV1%pred < 80, and DLCOc%pred < 80 was higher in T2DM subjects than controls (all P < 0.05). Subgroup analysis of diabetic patients showed that the values of FVC%pred, FEV1%pred, TLC%pred, and DLCOc%pred (97.18 ± 13.45, 93.95 ± 14.51, 90.64 ± 9.97, 87.27 ± 13.13, respectively) were significantly lower in T2DM subjects with albuminuria than those without albuminuria (103.94 ± 14.12, 99.20 ± 14.25, 93.79 ± 10.36, 92.62 ± 13.45, all P < 0.05). There was a significantly negative correlation between the urine albumin-to-creatinine ratio (UACR) and DLCOc%pred (r = − 0.143, P = 0.010) in spearman linear correlation test. In logistic regression analysis, the FVC%pred (OR 0.965, 95%CI 0.944–0.988), FEV1%pred (OR 0.975, 95%CI 0.954–0.996), and DLCOc%pred (OR 0.974, 95%CI 0.951–0.998) were independently associated with albuminuria after adjustments for smoking index, duration, HbA1c, FBG, and TG.ConclusionOur results demonstrated albuminuria is associated with a restrictive pulmonary function as well as pulmonary diffusion function in T2DM with preserved renal function, which remind us to be alert of the pulmonary function decline even in the early stage of DN.

Link of Oxidative stress to Pulmonary Functions Contributed by Matrix Metalloproteinase in South Indian Population-An Observational Study

Background and Aim: Oxidative stress plays a key role in the etiopathogenesis of several disease conditions and most commonly pulmonary diseases. Pulmonary tissues are susceptible to oxidative stress from ambient air pollution. Serum Malondialdehyde is a sensitive biomarker of oxidative stress. Oxidants also enhance proteinase mediated lung injury. In the current study we have aimed at correlating the serum Malondialdehyde levels with pulmonary functions and serum Matrix mettaloproteinase-9 levels in south Indian population. Methods: This was a cross sectional study conducted among healthy volunteers of age group 18 to 45 years. Pulmonary function tests of the subjects were recorded using computerised spirometry (SPIROLAB III). Serum malondialdehyde levels were estimated using Thiobarbituric acid Reactive Substances assay and serum Matrix metalloproteinase-9 levels were estimated by Enzyme linked Immunosorbent Assay. Results: Significant negative correlation was found between Malondialdehyde and FEV1/FVC ratio and significant positive correlation was found between serum malondialdehyde levels and Matrix metalloproteinase-9 levels. Individual link of Malondialdehyde levels and FEV1/FVC ratio, malondialdehyde levels and Matrix metalloproteinase-9 levels were established by linear regression analysis. Conclusion: Our results state that increased oxidative stress directly affects pulmonary functions and it also increases MMP-9 levels, which again lead to decline in pulmonary functions.

JA:2021-31. Does the Use of a Nasal Lavage Intervention Improve Pulmonary Function for Dairy Workers?

ABSTRACT Purpose: Dairy workers are at the frontline of exposure to bioaerosols, which typically contain bacteria and associated pro-inflammatory constituents (e.g., endotoxin). As such, dairy workers are at an increased risk for respiratory illness, most likely mediated through a strong proinflammatory response. Very few studies have systematically evaluated control strategies to reduce exposure and improve health. Given the challenges and limitations of implementing engineering controls, we propose the use of a low-cost and low-burden intervention. Hypertonic saline (HTS) was recently shown to attenuate inflammation in trauma patients. Here, we conducted an intervention to administer HTS in a nasal lavage to determine if the inflammatory response was mitigated and if the airway function improved among dairy workers. Methods: Ten participants were recruited from a large herd dairy and randomly assigned to treatment (n = 5) and control groups (n = 5). Each participant received normotonic saline (308 mOsm) nasal lavage (NL) before their shift over 5 consecutive days. After each shift, the treatment group received HTS, while the control group received normotonic saline. All samples were analyzed for 10 different cytokines using a multiplex assay. Spirometry was performed pre- and post-shift to examine forced expiratory volume in one second, forced vital capacity and the subsequent ratio, and peak expiratory flow rate (PEFR). Personal breathing zone samples for inhalable bioaerosols were collected across the work shift; mass concentrations and endotoxin abundance were determined by gravimetry and a fluorescent assay, respectively. Statistical analyses and models were performed using SAS. Results/Findings: Differences in pro-inflammatory cytokines were observed. There was an interaction effect on IL-10 between treatment, day, and time of day, indicating promotion of anti-inflammatory effect. The treatment group experienced an increase in PEFR change (0.76 L, p = 0.12) near statistical significance; no statistically significant differences were observed in the other spirometry measures. Both groups of dairy workers in this study experienced less of a decline in cross-shift pulmonary function when compared to other studies. Practical Application: The HTS nasal lavage is designed as a low-cost intervention that can be self-administered before and after every shift across other agricultural operations. This study was limited by small sample size and warrants further investigation.

Investigation of the Pulmonary Function Level in Municipal Solid Waste Collectors: A Case of Bandar Abbas City During 2015 - 2017

Background: In Iran, most of the cleaning processes are performed manually in urban areas. Sweepers are exposed to respiratory pollutants, infectious substances, and other hazardous substances such as chemicals, animal feces, and sharp objects during improper disposal of waste. Respiratory pollutants in these occupations can cause inflammation and damage to the respiratory system. Moreover, prolonged exposure to respiratory pollutants in the workplace can reduce lung function and cause numerous health problems. Objectives: This study aimed to examine the effect of workplace exposures of municipal solid waste collectors on the reduction of the pulmonary function level. Methods: This retrospective cohort study was performed on 198 municipal solid waste collectors aged 18 to 55 years who were employed in this profession for at least two years. The sampling method was census, and demographic data were extracted from occupational examination records. Results: Examining the relationship between pulmonary function decline and the studied variables showed a significant relationship between smoking and reduction of FVC, FEV1, and FEF25 -75. However, no significant relationship was observed between dust exposure and pulmonary function decline. Conclusions: No significant relationship was observed between pulmonary function loss and occupational dust exposure in municipal solid waste collectors. This means that the occupational exposure of these individuals was not severe enough to cause pulmonary function loss.

BASELINE CHARACTERISTICS OF ALL PATIENTS ENROLLED IN A PHASE II CLINICAL TRIAL ASSESSING THE EFFICACY AND SAFETY OF NINTEDANIB IN LYMPHANGIOLEIOMYOMATOSIS

TYPE: Abstract Publication TOPIC: Diffuse Lung Disease PURPOSE: Lymphangioleiomyomatosis (LAM) is a disease, mainly affecting women. It can be sporadic or associated to Tuberous Sclerosis (TSC). In the MILES trial, sirolimus, has been proven to be effective in the treatment of patients with LAM. Drug toxicity and resistance are problems related to sirolimus. Nintedanib is an inhibitor of the tyrosin kinase PDGF receptor (PDGFR) present and active in human and murine TSC lesions. The aim of this abstract is to report the baseline characteristics of all LAM patients enrolled in this trial investigating the efficacy and safety of nintedanib METHODS: 30 LAM patients showing a progressive pulmonary function decline in the last year or side effects and/or toxicities/contraindications to sirolimus. The protocol planned 12 months of treatmentwith nintedanib fand 12 month of follow up without treatment. The primary endpoint is the FEV1 response . RESULTS: Baseline characteristics of the pts are reported below and compared with those from the MILES trial. CONCLUSIONS: The results of this ongoing study will allow assessment of the impact of nintedanib in LAM patients CLINICAL IMPLICATIONS: DISCLOSURE: No significant relationships. KEYWORD: lymphangioleiomYomatosis; cistic lung disease

A Natural History Study of VCP Associated Vacuolar Myopathy in a Patient with the Common R155H Mutation

Background: IBMPFD (Inclusion Body Myopathy associated with Paget disease of the bone and Frontotemporal Dementia) is an autosomal dominant inherited disease caused by VCP gene mutations. Very little natural history data exists on this disease. We report a patient with a significant family history of IBMPFD associated with the common R155H mutation in the VCP gene. Objective: This study will address the lack of long-term data for muscle strength, and respiratory function in IBMPFD. The hypothesis is that detailed analysis in a single patient will provide meaningful natural history data in IBMPFD, a progressive neurodegenerative disease. Method: Regression analysis was performed across multiple parameters related to myopathy including dynamometry, MRC scale, IBM functional rating scale, pulmonary function studies and sleep quality. Results: Measurements of this patient highlight progressive generalized weakness in proximal and distal regions, decline in pulmonary function, and asymmetrical strength differences of the upper extremities. Measurements over five years revealed an overall deterioration with a slope of -1.13 and R2 value of 0.77. Conclusion: This unique data derived from long-term evaluations in a patient provides the first report of the rate of progression of muscle weakness and pulmonary function deterioration in VCP associated inclusion body myopathy.

Thymus and activation-regulated chemokine (TARC/CCL17) predicts decline of pulmonary function in patients with chronic obstructive pulmonary disease

BackgroundThe deterioration of pulmonary function, such as FEV1-decline, is strongly associated with poor prognosis in patients with chronic obstructive pulmonary disease (COPD). However, few investigations shed light on useful biomarkers for predicting the decline of pulmonary function. We evaluated whether thymus and activation-regulated chemokine (TARC), a Th2 inflammation marker, could predict rapid FEV1-decline in COPD patients. MethodsWe recruited 161 patients with stable COPD and performed pulmonary function test once every six months. At the time of registration, blood tests, including serum levels of TARC were performed. We assessed the correlation between changes in parameters of pulmonary function tests and serum levels of TARC. The rapid-decline in pulmonary function was determined using 25th percentile of change in FEV1 or FEV1 percent predicted (%FEV1) per year. ResultsIn the FEV1-rapid-decline group, the frequency of exacerbations, the degree of emphysema, and serum levels of TARC was higher than in the non-rapid-decline group. When using %FEV1 as a classifier instead of FEV1, age, the frequency of exacerbations, the degree of emphysema and serum levels of TARC in the rapid-decline group was significantly greater than those in the non-rapid-decline group. In univariate logistic regression analysis, TARC was the significant predictive factor for rapid-decline group. In multivariate analysis adjusted for emphysema, serum levels of TARC are independently significant predicting factors for the rapid-decline group. ConclusionsTARC is an independent predictive biomarker for the rapid-decline in FEV1. Measuring serum TARC levels may help the management of COPD patients by predicting the risk of FEV1 decline.

Pulmonary function decline in immediate postoperative period is not necessarily related to residual neuromuscular block

Previous studies have reported an association between the use of neuromuscular blocking (NMB) agents and postoperative pulmonary complications. Postoperative pulmonary function is a key indicator for postoperative pulmonary complications. Several sites can be used to assess depth and recovery from NMB. To investigate postoperative pulmonary function change in relation to train-of-four measurements at the adductor pollicis and corrugator supercilii muscles, and anaesthesia-related variables in orthopaedic patients undergoing hip or knee arthroplasty. Observational study. University hospital. Orthopaedic patients undergoing hip or knee arthroplasty. Postoperative pulmonary function tests in the postanaesthesia care unit. Patients scheduled for elective hip or knee arthroplasty received simultaneous corrugator supercilii and adductor pollicis measurements during anaesthesia conducted according to clinical standards. Forced expiratory volume in 1 s and forced vital capacity (FVC) were measured at the time of inclusion and postoperatively on the postanaesthesia care unit. Linear regression analysis was performed for association between risk factors and pulmonary function change. A total of 35 patients were included. After exclusions, 20 patients remained for final analysis. Corrugator supercilii showed earlier NMB recovery than adductor pollicis. FVC decreased significantly after surgery from 2.9 ± 1.0 to 2.3 ± 1.0 (P < 0.01) and forced expiratory volume in 1 s decreased from 2.3 ± 0.9 to 1.6 ± 0.8 l (P < 0.01). Patient age was the only factor significantly related to FVC decrease after surgery (P = 0.019) with a cut-off value of 65 years. Both corrugator supercilii and adductor pollicis failed to indicate recovery of pulmonary function after NMB. Age seems to be a risk factor for postoperative decline in pulmonary function. German Clinical Trials registry, DRKS-ID: DRKS00014305.

MON-LB114 CGM in Cystic Fibrosis Patients to Predict Cystic Fibrosis-Related Diabetes Onset

Background: Therapeutic progress and improvement on resources enabled the emergence of new comorbidities in cystic fibrosis (CF), such as cystic fibrosis-related diabetes (CFRD). About 20% of adolescents and 40-50% of adults are affected. CFRD and glucose intolerance reduce life expectancy in this population, highlighting the importance of early diagnosis and treatment. Up to 15% of CF patients have hypoglycemia during OGTT and its etiology remains unclear. Some authors associate hypoglycemia with CFRD onset, while others do not agree with this association. Objective: To determine whether abnormal CGM (hypo/hyperglycemia) can predict CFRD onset, pulmonary function and BMI decline in CF patients. Methods: Prospective single center study. All CF patients between 10-19yo from our outpatient clinic were screened for CFRD through OGTT following the World Health Organization (WHO) protocol. The enzymatic colorimetric method was used to classify them as per the ADA. Non-diabetic CF patients performed 3-day CGM, forced expiratory volume in the first second (FEV1), BMI and OGTT. All tests except for CGM were then reassessed after a long follow-up. The WHO’s 2006 curve was used to calculate the z scores for individuals ≤19yo and WHO cut-off values for >19yo. Oral corticoid use during data collection, pregnancy and solid organ transplantation were exclusion criteria. Results: Thirty-nine patients were recruited and 34 completed an average of 3.1 years (±0.51) follow-up. No clinical or laboratory variables could predict diabetes progression or hypoglycemic events. The cohort had an increase in mean BMI (17.80±3.65 vs 18.36±3.49; p=0.025) and a reduction in mean FEV1 (66.91±25.79% vs 56.32±29.57%; p=0.001) between the two evaluations. Patients who developed diabetes showed statistically significant worse FEV1 in the end of the follow-up (22.67±5 vs 59.58±28.9; p=0.041), and lower BMI at both start (14.37±1.23 vs 18.13±3.65; p=0.049) and end (14.81±0.66 vs 18.71±3.46; p=0.029) of follow-up. A logistic regression of the effect of time adjusted for independent variables for progression to CFRD was conducted. A higher possibility of evolution among participants with IGT (odds ratio [OR] 21.67; 95% confidence interval [CI] 7.03-67.36; p<0.01), and a lower possibility among participants with NGT (OR 1.84; 95% CI 1.06-3.19; p=0.031). Conclusion: CGM was not a useful tool to predict early diabetes onset in this population with the current cut-off values. However, the IGT group seems to be the riskiest group. The CF population has particular characteristics and may not have the same diagnostic criteria for DM as the non-CF population. More studies are necessary to determine the appropriate CGM cut-off values for CFRD.

Late-onset "acute fibrinous and organising pneumonia" impairs long-term lung allograft function and survival.

Acute fibrinous and organising pneumonia (AFOP) after lung transplantation is associated with a rapid decline in pulmonary function. However, the relation with chronic lung allograft dysfunction (CLAD) remains unclear. We investigated the association between detection of AFOP in lung allograft biopsies with clinically important endpoints.We reviewed lung allograft biopsies from 468 patients who underwent lung transplantation at the University Hospitals Leuven (2011-2017). AFOP was categorised as early new-onset (≤90 days post-transplant) or late new-onset (>90 days post-transplant); and associated with CLAD-free survival, graft survival, donor-specific antibodies, airway and blood eosinophilia.Early and late AFOP was detected in 24 (5%) and 30 (6%) patients, respectively. CLAD-free survival was significantly lower in patients with late AFOP (median survival 2.42 years; p<0.0001) compared with patients with early or without AFOP and specifically associated with development of restrictive allograft syndrome (OR 28.57, 95% CI 11.34-67.88; p<0.0001). Similarly, graft survival was significantly lower in patients with late AFOP (median survival 4.39 years; p<0.0001) compared with patients with early AFOP or without AFOP. Late AFOP was furthermore associated with detection of circulating donor-specific antibodies (OR 4.75, 95% CI 2.17-10.60; p=0.0004) compared with patients with early or without AFOP, and elevated airway and blood eosinophilia (p=0.043 and p=0.045, respectively) compared with early AFOP patients.Late new-onset AFOP is associated with a worse prognosis and high risk of CLAD development, specifically restrictive allograft syndrome. Our findings indicate that late new-onset AFOP might play a role in the early pathogenesis of restrictive allograft syndrome.