Moderate Lung Disease Research Articles

Post COVID lung fibrosis (PCLF) or post COVID lung sequelae (PCLS): Which one is the right choice?

Lung is the primary target organ in COVID-19 disease with diverse clinical and radiological presentations and outcome. It has caused minimal to moderate lung disease in some patients and in some cases caused deadly acute respiratory distress syndrome (ARDS). COVID-19 disease caused lung damage by direct virus induced alveolar damage, cytokine induced alveolar and vascular damage and microvascular thrombosis resulting into acute hypoxic respiratory failure. COVID-19 pneumonia evolved over period of three weeks in cases with ARDS as natural course of illness. Usually, ARDS resolves by fibrosis or resolution as final outcome. Similarly, in COVID-19 recovered cases of advanced disease or those suffering from ARDS are having post COVID lung disease. Lung fibrosis is final radiological outcome of COVID-19 pneumonia documented in proportionately majority of cases. Post COVID lung fibrosis is considered as worrisome radiological complication observed during early phase of pandemic. Time trends of final radiological outcome has evolved over months with or without treatment with antifibrotics and steroids. Importantly, Post COVID lung fibrosis resolved more than fifty percent cases in six months and nearly in all cases after one year. Post COVID lung fibrosis is considered as ‘health issue of great concern’ initially in post pandemic phase of first wave, and due to its resolving nature over time period; now considered as ‘sigh with relief’ due to its reversible pathophysiology. Post COVID sequel is minimal residual effects of COVID-19 lung disease irrespective of disease severity in past. We recommend to use term post COVID sequel over post COVID lung fibrosis.

Nintedanib as an Antifibrotic in Post Covid Lung Fibrosis: Are we Really Overestimating?

Antifibrotics were exuberantly used to treat post covid lung complications. Lung is the primary target organ in COVID-19 disease with diverse clinical and radiological presentations and outcome. It has caused minimal to moderate lung disease in some patients and in some cases caused deadly acute respiratory distress syndrome (ARDS). COVID-19 disease caused lung damage by direct virus induced alveolar damage, cytokine induced alveolar and vascular damage and microvascular thrombosis resulting into acute hypoxic respiratory failure. COVID-19 pneumonia evolved over period of three weeks in cases with ARDS as natural course of illness. Usually, ARDS resolves by fibrosis or resolution as final outcome. Similarly, in COVID-19 recovered cases of advanced disease or those suffering from ARDS are having post covid lung disease. Lung fibrosis is final radiological outcome of COVID-19 pneumonia documented in proportionately majority of cases. Post COVID lung fibrosis is considered as worrisome radiological complication observed during early phase of pandemic. Antifibrotics such as Nintedanib and Pirfenidone were used to treat post covid lung complications such as fibrosis. Both drugs were shown good antifibrotic property in clinical trials for fibrotic lung disease and observed positive outcome in restoring lung parenchyma. Time trends of final radiological outcome has evolved over months with or without treatment with antifibrotics and steroids. Importantly, Post covid lung fibrosis resolved more than fifty percent cases in six months and nearly in all cases after one year. Thus, antifibrotics were used irrationally in fibrosing lung condition of reversible type. Actually, we have overestimated post covid lung fibrosis and overtreated with antifibrotics.

Subtyping preserved ratio impaired spirometry (PRISm) by using quantitative HRCT imaging characteristics

BackgroundPreserved Ratio Impaired Spirometry (PRISm) is defined as FEV1/FVC ≥ 70% and FEV1 < 80%pred by pulmonary function test (PFT). It has highly prevalence and is associated with increased respiratory symptoms, systemic inflammation, and mortality. However, there are few radiological studies related to PRISm. The purpose of this study was to investigate the quantitative high-resolution computed tomography (HRCT) characteristics of PRISm and to evaluate the correlation between quantitative HRCT parameters and pulmonary function parameters, with the goal of establishing a nomogram model for predicting PRISm based on quantitative HRCT.MethodsA prospective and continuous study was performed in 488 respiratory outpatients from February 2020 to February 2021. All patients underwent both deep inspiratory and expiratory CT examinations, and received pulmonary function test (PFT) within 1 month. According to the exclusion criteria and Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification standard, 94 cases of normal pulmonary function, 51 cases of PRISm and 48 cases of mild to moderate chronic obstructive lung disease (COPD) were included in the study. The lung parenchyma, parametric response mapping (PRM), airway and vessel parameters were measured by automatic segmentation software (Aview). One-way analysis of variance (ANOVA) was used to compare the differences in clinical features, pulmonary function parameters and quantitative CT parameters. Spearman rank correlation analysis was used to evaluate the correlation between CT quantitative index and pulmonary function parameters. The predictors were obtained by binary logistics regression analysis respectively in normal and PRISm as well as PRISm and mild to moderate COPD, and the nomogram model was established.ResultsThere were significant differences in pulmonary function parameters among the three groups (P < 0.001). The differences in pulmonary parenchyma parameters such as emphysema index (EI), pixel indices-1 (PI-1) and PI-15 were mainly between mild to moderate COPD and the other two groups. The differences of airway parameters and pulmonary vascular parameters were mainly between normal and the other two groups, but were not found between PRISm and mild to moderate COPD. Especially there were significant differences in mean lung density (MLD) and the percent of normal in PRM (PRMNormal) among the three groups. Most of the pulmonary quantitative CT parameters had mild to moderate correlation with pulmonary function parameters. The predictors of the nomogram model using binary logistics regression analysis to distinguish normal from PRISm were smoking, MLD, the percent of functional small airways disease (fSAD) in PRM (PRMfSAD) and Lumen area. It had a good goodness of fit (χ2 = 0.31, P < 0.001) with the area under curve (AUC) value of 0.786. The predictor of distinguishing PRISm from mild to moderate COPD were PRMEmph (P < 0.001, AUC = 0.852).ConclusionsPRISm was significantly different from subjects with normal pulmonary function in small airway and vessel lesions, which was more inclined to mild to moderate COPD, but there was no increase in pulmonary parenchymal attenuation. The nomogram based on quantitative HRCT parameters has good predictive value and provide more objective evidence for the early screening of PRISm.

A survey: Understanding the health and perspectives of people with CF not benefiting from CFTR modulators.

BackgroundWhile the advent of cystic fibrosis transmembrane conductance regulator (CFTR) modulator use has improved daily life and long‐term prognosis of CF for many with approved CFTR mutations, approximately 10% of people with CF (pwCF) have only symptomatic treatments available.MethodsBetween June 10 and July 1, 2021, Emily's Entourage distributed a 38‐question anonymous survey targeted at pwCF not benefitting from approved modulators via social media and email to pwCF and CF advocacy groups in and outside the United States regarding health status, impact of CF, unmet needs, and clinical research interest.ResultsThere were 431 survey respondents representing pwCF on five continents. The majority of pwCF had moderate lung disease (50.3%). Ineligibility based on CFTR mutation (64.1%) was the most frequently reported reason pwCF were not on modulators. PwCF reported the most impacted aspects of life were mental (66.7%) and physical (40.7%) health. Financial concerns and feelings of isolation were commonly reported. Witnessing improvements for peers with access to modulators was both uplifting and disheartening. The majority of pwCF would be interested in participating in future clinical research (77.6%), although some living outside of the United States cited lack of opportunity to participate in clinical trials as a barrier.ConclusionsPwCF who are ineligible, intolerant, or lack access to modulators have a high burden of disease impacting their physical and mental health. Although most are happy for those who are benefiting from modulators, they are eager for the opportunity to experience similar improvements for themselves, and willing to participate in clinical trials of new therapies.

Controlled inhalation improves central and peripheral deposition in cystic fibrosis patients with moderate lung disease.

AimWith progressive impairment of lung function, deposition of inhaled drug in the lungs becomes progressively more central, limiting its effectiveness. This pilot study explored the possibility that long slow inhalations might improve delivery of aerosol to the lung periphery in cystic fibrosis patients with moderate lung disease.MethodsFive subjects aged 12–18 years (mean FEV1 72%; range 63–80%) inhaled a radiolabelled aerosol from a jet nebuliser on two occasions. Two inhalation techniques were compared: breathing tidally from a standard continuous output nebuliser and using long slow inhalations from the AKITA® JET system.ResultsLong slow breaths resulted in much lower oropharyngeal deposition with higher lung doses. Importantly, the peripheral lung increased proportionately. The increased lung dose is attributable to more of the larger inhaled droplets passing into the lower airways. This would be expected to increase the central deposition unless significantly more of the smaller droplets were able to penetrate deeper into the lungs. The data support improved delivery of drug to the distal lung when compared with tidal breathing.ConclusionThese pilot data suggest that this approach may prove to be clinically relevant in improving the efficacy of inhaled medication in those with moderate‐severe lung disease.

EPIDERMOLYSIS BULLOSA ACQUISITA PRESENTING WITH USUAL INTERSTITIAL PNEUMONIA AND PNEUMOMEDIASTINUM

TOPIC: Pulmonary Manifestations of Systemic Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: Epidermolysis Bullosa Acquisita (EBA) is an autoimmune disease which presents with chronic blistering and scarring of the skin and mucous membranes. We present a case of EBA presenting with Usual Interstitial Pneumonia (UIP) and pneumomediastinum;an extremely rare complication. CASE PRESENTATION: An 84 year-old man presented to the emergency department with worsening dyspnea and multiple blistering lesions along with associated fatigue and weight loss for approximately 6 months. Past medical history was significant for previously diagnosed EBA, hypertension and hyperlipidemia. The patient is a Veteran and retired salesman who denied hazardous occupational exposure. Physical examination revealed bilaterally decreased breath sounds and also multiple crusted blisters in all four extremities. COVID test was negative and initial laboratory panel was only remarkable for mild macrocytic anemia. Outpatient chest radiograph obtained ten days prior to admission (fig 1) and repeat on admission showed bilateral interstitial reticulonodular opacities with new asymmetric opacifications in the right lung apex (fig 2). Chest CT angiogram demonstrated fibrotic changes and honeycombing in the peripheries and bases with moderate pneumomediastinum (fig 3). He was diagnosed with UIP given the radiologic pattern and this was attributed to be likely due to his current EBA flare-up given no other obvious trigger. The patient's home dose of dapsone for EBA was continued and he was given nebulized bronchodilators with improvement in his symptoms over 48 hours. Pulmonology was consulted and recommended outpatient follow up in 3 weeks as he remained hemodynamically stable and was saturating well on room air. Repeat Chest CT on follow up showed improvement of the pneumomediastinum (fig 4). Pulmonary function tests showed moderate restrictive lung disease with moderately reduced diffusing capacity, however his symptoms were mostly resolved. DISCUSSION: EBA is an orphan autoimmune whose pathophysiology involves auto-antibodies against type VII collagen (COL7). These create a specific u-serrated pattern on peri-lesional skin biopsies [1]. COL7 is also known to be a component of the pulmonary basement membrane;with collagen accounting for a third of the dry mass of the lung. EBA has been weakly associated with multiple autoimmune diseases including anecdotal reports of association with pulmonary fibrosis [2]. However extensive review of literature showed no published case reports connecting the two conditions. In our opinion, this patient's presentation is likely a result of the interaction of COL7 antibodies with the pulmonary basement membrane leading to UIP with pneumomediastinum. CONCLUSIONS: This case highlights the rare association between EBA and UIP which are likely connected pathophysiologically by anti-COL7 antibodies. Further research and analysis will be needed to confidently establish this association. REFERENCE #1: Koga H, Prost-Squarcioni C, Iwata H, Jonkman MF, Ludwig RJ, Bieber K. Epidermolysis Bullosa Acquisita: The 2019 Update. Front Med (Lausanne). 2019;5:362. Published 2019 Jan 10. doi:10.3389/fmed.2018.00362 REFERENCE #2: Gupta R, Woodley DT, Chen M. Epidermolysis bullosa acquisita. Clin Dermatol. (2012) 30:60–9. 10.1016/j.clindermatol.2011.03.011 DISCLOSURES: no disclosure on file for Kay Khine;No relevant relationships by Natarajan Rajagopalan, source=Web Response No relevant relationships by Karan Soni, source=Web Response

NOT ALL THE PATIENTS PRESENTING WITH SHORTNESS OF BREATH HAVE HEART OR LUNG DISEASES

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: The diaphragm is the primary muscle of respiration. Patients with bilateral diaphragmatic paralysis can present with dyspnea on exertion and be misdiagnosed as acute heart failure. Thyroid myopathy can involve diaphragm and require a high index of suspicion in patients with symptoms of heart failure with negative workup. CASE PRESENTATION: A 47-year-old male with a past medical history of coronary artery bypass grafting, and heart failure presented with dyspnea on exertion and orthopnea for one month. He was recently admitted with the same complaints and was discharged on an increased dose of furosemide with no response. On presentation, physical exam revealed orthopnea and bilateral decreased air entry at the lung bases. Oxygen saturation was 86% on room air. Arterial blood gas results showed pH 7.31, PCO2 61 on 100% FIO2. Laboratory data, including complete blood count and comprehensive metabolic profile, were unremarkable. EKG showed normal sinus rhythm and transthoracic echocardiogram showed an ejection fraction of 62%. Chest x-ray showed elevation of right hemidiaphragm (figure-1). He was treated with intravenous Lasix and BiPAP, but symptoms didn't improve, which prompted further workup, including a fluoroscopic "sniff test," which showed the paradoxical motion of both hemidiaphragm consistent with diaphragmatic paralysis. TSH level came back 306.0 µIU/ml, free T4 level was 0.32 ng/dL. Pulmonary function tests depicted mild obstructive and moderate restrictive lung disease (figure-2). Pt was treated with levothyroxine and was discharged on levothyroxine and trilogy after symptoms started improving. He showed significant improvement at one month's follow-up. DISCUSSION: Bilateral diaphragmatic paralysis primarily presents with shortness of breath on exertion and orthopnea within minutes of recumbency. The diagnosis is challenging as symptoms can be misinterpreted as a sign of heart failure; hence it is prudent to rule out acute heart failure. Severe hypothyroidism presenting as bilateral diaphragmatic paralysis is rarely reported in the literature, which decreases the activity of acid maltase, causing thyroid myopathy. The diagnosis can be made by paradoxical motion of hemidiaphragm on "sniff test," however, the measurement of trans-diaphragmatic pressure is the gold standard. The treatment depends on etiology and severity. Hypothyroidism should be treated promptly, and the use of small portable ventilators such as trilogy are helpful to assist breathing. In patients with intact phrenic nerve with no myopathy, phrenic nerve pacing can also be considered. CONCLUSIONS: Signs and symptoms of diaphragmatic paralysis can mimic heart failure. Physicians should maintain a high index of suspicion to workup for hypothyroidism and paralysis of the diaphragm in patients with typical presentation in the absence of cardiac or pulmonary etiology, as early diagnosis and treatment have good outcomes. REFERENCE #1: Thulaseedharan NK, Geetha P, Arathi N, et al. An unusual cause of orthopnoea-hashimoto's thyroiditis presenting as bilateral diaphragmatic palsy. Respiratory Medicine Case Reports. 2017;21:132-134. doi:10.1016/j.rmcr.2017.04.016 DISCLOSURES: No relevant relationships by Shaji Baig, source=Web Response No relevant relationships by Aneeba FAROOQi, source=Web Response No relevant relationships by Hafiz Jeelani, source=Web Response

Factors for severe outcomes following SARS-CoV-2 infection in people with cystic fibrosis in Europe.

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in people with cystic fibrosis (pwCF) can lead to severe outcomes.MethodsIn this observational study, the European Cystic Fibrosis Society Patient Registry collected data on pwCF and SARS-CoV-2 infection to estimate incidence, describe clinical presentation and investigate factors associated with severe outcomes using multivariable analysis.ResultsUp to December 31, 2020, 26 countries reported information on 828 pwCF and SARS-CoV-2 infection. Incidence was 17.2 per 1000 pwCF (95% CI: 16.0–18.4). Median age was 24 years, 48.4% were male and 9.4% had lung transplants. SARS-CoV-2 incidence was higher in lung-transplanted (28.6; 95% CI: 22.7–35.5) versus non-lung-transplanted pwCF (16.6; 95% CI: 15.4–17.8) (p≤0.001).SARS-CoV-2 infection caused symptomatic illness in 75.7%. Factors associated with symptomatic SARS-CoV-2 infection were age >40 years, at least one F508del mutation and pancreatic insufficiency.Overall, 23.7% of pwCF were admitted to hospital, 2.5% of those to intensive care, and regretfully 11 (1.4%) died. Hospitalisation, oxygen therapy, intensive care, respiratory support and death were 2- to 6-fold more frequent in lung-transplanted versus non-lung-transplanted pwCF.Factors associated with hospitalisation and oxygen therapy were lung transplantation, cystic fibrosis-related diabetes (CFRD), moderate or severe lung disease and azithromycin use (often considered a surrogate marker for Pseudomonas aeruginosa infection and poorer lung function).ConclusionSARS-CoV-2 infection yielded high morbidity and hospitalisation in pwCF. PwCF with forced expiratory volume in 1 s <70% predicted, CFRD and those with lung transplants are at particular risk of more severe outcomes.

Performance Evaluation of Nasal Prong Interface for CPAP Delivery on a Critical Care Ventilator: A Bench Experiment.

The RAM cannula (Neotech, Valencia, CA) has become a commonly used interface for CPAP in neonatal intensive care. Performance characteristics of this interface used with a critical care ventilator are not well described. This was a bench study utilizing a lung simulator configured as an actively breathing infant (weights of 800 g, 1.5 kg, and 3 kg) with moderate lung disease and a critical care ventilator in CPAP mode with leak compensation on. Three sizes of the RAM cannulae (preemie, newborn, and infant) were compared to 3 BabyFlow nasal prongs (Dräger Medical, Lübeck, Germany) (medium, large, and extra-large). Fabricated nasal models produced a 70% occlusive fit for the RAM cannula and an occlusive fit with the Dräger prongs. Delivered flow and pressure levels were recorded at 9 CPAP levels between 5 and 20 cm H2O. The Dräger prongs produced a mean airway pressure ([Formula: see text]) within 0.20 cm H2O (range -0.10 to 0.35) of the set CPAP across all evaluated prong sizes and CPAP levels. In contrast, the RAM cannula produced [Formula: see text] values that averaged 8.5 cm H2O (range -15 to -3.5) below the set CPAP levels. The deficit in delivered versus target CPAP level for the RAM cannula increased with greater set CPAP. Set CPAP of 5 cm H2O delivered [Formula: see text] values that ranged from 0.6 to 1.5 cm H2O (difference of 3.5-4.4 cm H2O). Set CPAP of 20 cm H2O delivered [Formula: see text] values that ranged from 5.0 to 8.4 cm H2O (difference of 11.7-15 cm H2O). Inspiratory flow required to achieve set CPAP levels did not differ between interfaces, suggesting high resistance in the RAM cannula device masks the delivered CPAP levels. Use of the RAM cannula with a 30% leak on a critical care ventilator delivered [Formula: see text] values lower than set CPAP. This may be clinically meaningful and should be considered when choosing a nasal interface.

Real-world assessment of LCI following lumacaftor-ivacaftor initiation in adolescents and adults with cystic fibrosis

Lung clearance index (LCI) is a biomarker of ventilation inhomogeneity. Data are scarce on its usefulness in daily practice for monitoring the effects of treatments in older children and adults with CF. In this French observational study of lumacaftor-ivacaftor, 63 of 845 patients (7.5%) had available LCI performed at baseline and at six (M6; n=34) or 12 months (M12; n=46) after lumacaftor-ivacaftor initiation. At inclusion, median [IQR] age was 16 years [13-17], ppFEV1 was 72.8 [59.6-80.7], and LCI was 12.3 [10.3-15.0]. At both M6 and M12, no statistically significant LCI increases of 0.13 units or 1.34% (95% CI: -4.85-7.53) and 0.6 units or 6.66% (95% CI: -0.03-13.5) were observed. Discordant results between LCI and ppFEV1 were observed in one-third of the patients. In daily practice, LCI monitoring in adolescents and young adults with moderate lung disease gives results that are more heterogenous than those reported in children with milder disease.

Phenotypic characteristics of incident and chronic MRSA isolates in cystic fibrosis

BackgroundChronic methicillin resistant Staphylococcus aureus (MRSA) in CF is associated with worse outcomes compared to early or intermittent infection. This observation could be related to adaptive bacterial changes such as biofilm formation or anaerobic growth. MethodsMRSA isolates stored from incident and during chronic (>2 years) infection were included at two study sites. MRSA isolates were characterised by spa-typing, antimicrobial susceptibility testing, biofilm formation and haemolysis under aerobic and anaerobic culture conditions. ResultsPaired MRSA isolates from 49 patients were included. Mean age at incident infection was 9.7±1.2 years with mild to moderate lung disease (FEV1 74±4% predicted). Twenty-five subjects showed progression of disease/symptoms after onset of MRSA with significantly increased use of antibiotics. Most isolates belonged to t002 (38%) and t008 (36%) spa-types and 8 patients had a change in spa-type over time. Antimicrobial susceptibility testing showed few differences between incident and late isolates but significantly lower MIC under anaerobic vs. aerobic conditions for vancomycin, fusidic acid, rifampin but higher MIC for trimethoprim-sulfamethoxazole. Biofilm formation and haemolysis did not differ by stage of infection or disease course but both were lower under anaerobic conditions (biofilm p=0.018; haemolysis p=0.002) in multi-variate analyses that included study site, growth condition and stage of infection. ConclusionsPersistent MRSA infection is frequently associated with clinical decline. Anaerobic growth conditions, which occur in CF airways, affect the expression of virulence factors and antibiotic susceptibility of MRSA more than duration of infection.

Changes in Pulmonary Function and Development of Clinical Radiation Pneumonitis in Breast Cancer Patients following Post Mastectomy Radiation Therapy

Background: Lung is the main organ at risk for radiation induced injury while treating breast cancers with Post Mastectomy Radiotherapy (PMRT). Restrictive lung changes are usually seen in spirometry which tends to normalize by 1 year. Central Lung Distance (CLD) is shown to correlate well with the percentage of ipsilateral lung volume irradiated. Aims and Objectives: Spirometric changes following Radiation Therapy (RT) to chest wall in breast cancer patients using conventional fractionation and its correlation with acute radiation pneumonitis. Materials and Methodology: Thirty Breast cancer patients who received RT to chest wall +/- supraclavicular fossa and axilla, following Modified Radical Mastectomy (MRM) and neoadjuvant or adjuvant chemotherapy using tangential beams with Co60 teletherapy to a dose of 50 Gray in conventional fractionation were included and followed up till 6 months post RT. Baseline chest X-ray and spirometry done pre-RT were compared with those taken at 1, 3 and 6 months after completion of RT. Patients were evaluated at each visit for signs and symptoms of radiation pneumonitis, when present were graded as per Radiation Therapy Oncology Group (RTOG) criteria. Results: There was a significant fall in Forced Vital Capacity (FVC) by the end of 3 months (p value &lt;0.01) which improved by 6 months without any active intervention in 95% of the patients. Mean baseline FVC was 83% which decreased to 70% by the end of 3 months and 79% at 6 months. Forced Expiratory Volume in first second (FEV1) and FEV1/FVC did not show any significant change compared to baseline. Spirometric changes correlated with reversible restrictive lung changes. One out of 30 patients developed symptomatic acute radiation pneumonitis (5%) of grade 3 severity who had moderate restrictive lung disease. Conclusion: Significant decrease in FVC of the lungs is present following PMRT in carcinoma of breast patients in the initial 3 months which tends to normalize by 6 months. 5% of the patients develop symptomatic acute lung toxicity which can be further reduced by minimizing the irradiated lung volume.

RAPIDLY PROGRESSIVE INTERSTITIAL LUNG DISEASE IN ASSOCIATION WITH MDA5 ANTIBODY DERMATOMYOSITIS

SESSION TITLE: Medical Student/Resident Diffuse Lung Disease SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Clinically Amyopathic Dermatomyositis (CADM) is a subtype of dermatomyositis (DM) characterized by the presence of cutaneous lesions, without clinical evidence of muscle weakness. The presence of autoantibodies against Melanoma Differentiation-Associated protein 5 (MDA5) in this group is highly associated with rapidly progressive interstitial lung disease (RP-ILD) and a worse prognosis. We present a case of anti-MDA5 associated RP-ILD to illustrate the importance of screening for MDA5 in patients with CADM and DM. CASE PRESENTATION: Our patient was a 45-year-old woman with a history of hypothyroidism, seronegative inflammatory polyarthritis treated with hydroxychloroquine, and notably, a history of biopsy-proven DM with a negative myositis-specific antibodies (MSA) panel (which did not include MDA5 antibodies). She had been successfully treated for DM, and maintained in remission with oral steroids. Four years following the diagnosis of DM, she presented with insidious and gradually progressive dyspnea for over a year. Physical examination was unremarkable. Pulmonary function testing showed moderate restrictive lung disease. Chest X-ray was notable for bibasilar interstitial changes. Computed tomography (CT) scan of the chest revealed nonspecific, bilateral ground-glass opacities in the middle and lower lung zones, with associated bibasilar bronchiectasis in the affected areas (Figure 1). Bronchoscopic evaluation, including transbronchial biopsy, was performed, which was negative for malignancy or infection. Open lung biopsy was obtained via robotic-assisted thoracoscopy from the affected lobes, with histopathology revealing interstitial fibrosis with multiple fibrotic foci without clear evidence of honeycombing. The pattern was suggestive of usual interstitial pneumonia (UIP). Repeat testing for MSA revealed an elevated anti-MDA5 antibody level at 22 SI. The patient was consequently diagnosed with RP-ILD in conjunction with CADM, prompting the initiation of oral prednisone and azathioprine. DISCUSSION: Anti-MDA5 antibodies recognize the RNA helicase encoded by MDA5, a protein that is involved in innate immune processes. The presence of anti-MDA5 antibodies in patients with CADM has been linked to the presence of RP-ILD, and portends a poor prognosis. The mechanism of this autoantibody production is not fully understood. One meta-analysis found that the presence of these antibodies was 77% sensitive and 86% specific for the identification of RP-ILD. Additionally, anti-MDA5 antibodies can be utilized to predict clinical outcomes and monitor disease activity in these patients. Due to its high mortality rate from respiratory failure, immediate therapy with high-intensity combination immunosuppression is essential once the diagnosis is made. CONCLUSIONS: This case highlights the importance of screening for anti-MD5 antibodies in patients with CADM to elucidate their risk of developing RP-ILD. Reference #1: Li L, Wang Q, Yang F, et al. Anti-MDA5 antibody as a potential diagnostic and prognostic biomarker in patients with dermatomyositis. Oncotarget. 2017;8(16):26552–26564. doi:10.18632/oncotarget.15716 Reference #2: Chen, Z., Cao, M., Plana, M.N., Liang, J., Cai, H., Kuwana, M. and Sun, L. (2013), Utility of Anti–Melanoma Differentiation–Associated Gene 5 Antibody Measurement in Identifying Patients With Dermatomyositis and a High Risk for Developing Rapidly Progressive Interstitial Lung Disease: A Review of the Literature and a Meta-Analysis. Arthritis Care & Research, 65: 1316-1324. doi:10.1002/acr.21985 DISCLOSURES: No relevant relationships by Komal Ejaz, source=Web Response No relevant relationships by Dan Kazmierski, source=Web Response No relevant relationships by Bassel Noumi, source=Web Response No relevant relationships by Pius Ochieng, source=Web Response No relevant relationships by NISHANT SHARMA, source=Web Response No relevant relationships by Yichen Wang, source=Web Response

A RARE CASE OF INTERSTITIAL LUNG DISEASE IN SYSTEMIC LUPUS ERYTHEMATOSUS

SESSION TITLE: Medical Student/Resident Pulmonary Manifestations of Systemic Disease Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Systemic lupus erythematosus (SLE) interstitial lung disease (ILD) is a spectrum of disease that is further characterized by histopathology. Among the literature, usual interstitial pneumonia (UIP) appears to be the rarest form. We present a case of a young female with this rare phenomenon. CASE PRESENTATION: A 38 year old female with a history of SLE was evaluated by pulmonology outpatient for progressively worsening dyspnea on exertion. Rest relieved the dyspnea and she could walk approximately 30 feet before having to stop. CT pulmonary angiography was negative for pulmonary emboli but showed peripheral interstitial markings bilaterally, greatest in the lower lobes. Pulmonary function test showed mild to moderate restrictive lung disease. Bronchoscopy, transbronchial biopsy, and serologic workup was negative except for elevated ANA. Since her diagnosis of SLE, she only had known joint involvement. ANA titer was 1:320. A repeat CT chest several months later showed subpleural interstitial markings within both upper lobe zones and more pronounced at the bases. CT surgery evaluated her and performed a video assisted thoracoscopy with biopsy of lower lung. Biopsy revealed a honeycomb pattern suggestive of UIP and idiopathic pulmonary fibrosis (IPF). A second opinion by a pathologist at a large academic center confirmed the initial diagnosis. She required supplemental oxygen for hypoxia on exertion and started mycophenolate with eventual addition of pirfenidone. Her symptoms improved and she is being evaluated for lung transplantation. DISCUSSION: Although SLE-UIP is rare, clinicians should remain diligent about thoroughly reviewing past medical history and having a broad differential for patients presenting with dyspnea. SLE-UIP has multiple forms including acute, subacute, and chronic although most cases have non-specific findings on high resolution CT or histopathology to subclassify the disease [1]. The prognosis is better than IPF/UIP associated with other connective tissue diseases [1,2,3] with a 5 year mortality rate of approximately 85% [1]. Literature on SLE-UIP is predominantly case reports and the ideal treatment has not been identified but most patients receive glucocorticosteroids with addition of immunsuppressive therapy if needed. In our patient, perhaps she will receive a lung transplant. CONCLUSIONS: Usual interstitial pneumonia in the setting of systemic lupus erythematosus is uncommon with few reported cases. To optimize treatment, further studies are warranted. Reference #1: Enomoto N, Egashira R, Tabata K, et al. Analysis of systemic lupus erythematosus-related interstitial pneumonia: a retrospective multicentre study. Sci Rep. 2019;9(1):7355. Reference #2: Nakamura Y, Chida K, Suda T, et al. Nonspecific interstitial pneumonia in collagen vascular diseases: comparison of the clinical characteristics and prognostic significance with usual interstitial pneumonia. Sarcoidosis Vasc Diffuse Lung Dis. 2003;20(3):235-41. Reference #3: Enomoto N, Suda T, Kato M, et al. Quantitative analysis of fibroblastic foci in usual interstitial pneumonia. Chest. 2006;130(1):22-9. DISCLOSURES: No relevant relationships by Bharat Avirneni, source=Web Response No relevant relationships by Christopher Rosse, source=Web Response No relevant relationships by Christopher Schmitt, source=Web Response

Correlation of dosimetric factors with the development of symptomatic radiation pneumonitis in stereotactic body radiotherapy

BackgroundThe development of radiation pneumonitis (RP) after Stereotactic Body Radiotherapy (SBRT) is known to be associated with many different factors, although historical analyses of RP have commonly utilized heterogeneous fractionation schemes and methods of reporting. This study aims to correlate dosimetric values and their association with the development of Symptomatic RP according to recent reporting standards as recommended by the American Association of Physicists in Medicine.MethodsWe performed a single-institution retrospective review for patients who received SBRT to the lung from 2010 to 2017. Inclusion criteria required near-homogeneous tumoricidal (α/β = 10 Gy) biological effective dose (BED10) of 100–105 Gy (e.g., 50/5, 48/4, 60/8), one or two synchronously treated lesions, and at least 6 months of follow up or documented evidence of pneumonitis. Symptomatic RP was determined clinically by treating radiation oncologists, requiring radiographic evidence and the administration of steroids. Dosimetric parameters and patient factors were recorded. Lung volumes subtracted gross tumor volume(s). Wilcoxon Rank Sums tests were used for nonparametric comparison of dosimetric data between patients with and without RP; p-values were Bonferroni adjusted when applicable. Logistic regressions were conducted to predict probabilities of symptomatic RP using univariable models for each radiation dosimetric parameter.ResultsThe final cohort included 103 treated lesions in 93 patients, eight of whom developed symptomatic RP (n = 8; 8.6%). The use of total mean lung dose (MLD) > 6 Gy alone captured five of the eight patients who developed symptomatic RP, while V20 > 10% captured two patients, both of whom demonstrated a MLD > 6 Gy. The remaining three patients who developed symptomatic RP without exceeding either metric were noted to have imaging evidence of moderate interstitial lung disease, inflammation of the lungs from recent concurrent chemoradiation therapy to the contralateral lung, or unique peri-tumoral inflammatory appearance at baseline before treatment.ConclusionsThis study is the largest dosimetric analysis of symptomatic RP in the literature, of which we are aware, that utilizes near-homogenous tumoricidal BED fractionation schemes. Mean lung dose and V20 are the most consistently reported of the various dosimetric parameters associated with symptomatic RP. MLD should be considered alongside V20 in the treatment planning process.Trial registrationRetrospectively registered on IRB 398–17-EP.

Prevalence and Risk Factors for Iron Deficiency in Adults With Cystic Fibrosis.

Iron deficiency is common in cystic fibrosis (CF), but previous prevalence studies often reported results confounded by acute exacerbations. This single-center retrospective study aimed to identify the prevalence of iron deficiency in a stable adult CF population, identify the risk factors associated with iron deficiency, and compare common laboratory indicators of iron status. Medical charts of 105 patients aged 18-67 were reviewed to determine the prevalence of anemia. Of these patients, a subgroup of 67 were included in analyses of iron deficiency, defined as serum ferritin < 12 ng/mL and/or percent transferrin saturation (TSAT) < 16%. Data on sex, age, body mass index, anemia status, vitamin deficiencies, presence of comorbidities, colonization with Pseudomonas aeruginosa, and use of acid blockers and CF transmembrane conductance regulator modulators were collected to evaluate relationship of iron deficiency with these clinical factors. κ agreements between serum iron, ferritin, transferrin, and TSAT were compared. In this stable CF population, the prevalence of iron deficiency was 41.8% (n = 67), and the prevalence of anemia was 33.3% (n = 105). Iron deficiency was associated with presence of anemia (P < .001), vitamin A deficiency (P = .012), and moderate (P = .047) and severe lung disease (P = .045) compared with mild lung disease. Transferrin agreed poorly with other iron status indicators. Iron deficiency is common in CF, although prevalence rates can vary widely depending on the laboratory parameters used. CF centers should consider routine screening for iron deficiency.

The role of pulmonary arterial hypertension-targeted therapy in systemic sclerosis.

Pulmonary arterial hypertension, categorized as group 1 pulmonary hypertension by the World Health Organization classification system, represents a major complication of systemic sclerosis resulting from pulmonary vascular involvement of the disease. The high mortality seen in systemic sclerosis-associated pulmonary arterial hypertension is likely due to the impairment of right ventricular systolic function and the coexistence of other non-group-1 pulmonary hypertension phenotypes that may negatively impact clinical response to pulmonary arterial hypertension-targeted therapy. This review highlights two areas of recent advances regarding the management of systemic sclerosis patients with pulmonary hypertension: the tolerability of pulmonary arterial hypertension-targeted therapy in the presence of mild to moderate interstitial lung disease and the potential clinical significance of the antifibrotic effect of soluble guanylate cyclase stimulators demonstrated in preclinical studies.

Ventilation efficiency to exercise in patients with cystic fibrosis.

Exercise ventilation efficiency index in cardiopulmonary exercise testing (CPET) is elevated in patients with heart failure providing useful information on disease progression and prognosis. Few data, however, exist for ventilation efficiency index among cystic fibrosis (CF) patients. To assess ventilation efficiency index (ΔVE/ΔVCO2 or V'E/V'CO2 slope) and intercept of ventilation (VE-intercept) in CF patients with mild, moderate, and severe cystic fibrosis (CF) lung disease. To assess possible correlations with ventilation inhomogeneity and structural damages as seen on high resolution computed tomography (HRCT). CF patients with mild (FEV1 > 80%, n = 47), moderate (60% < FEV1 < 80%, n = 21), and severe (FEV1 < 60%, n = 9) lung disease, mean age 14.9 years participated. Peak oxygen uptake (VO2 peak), pulmonary ventilation at peak exercise (VE), respiratory equivalent ratios for oxygen and carbon dioxide at peak exercise (VE/VO2 , VE/VCO2 ), end-tidal CO2 (PetCO2 ), and ΔVE/ΔVCO2 , ΔVE/ΔVO2 in a maximal CPET along with spirometry and multiple breath washout indices were examined. HRCT scans were performed and scored using Bhalla score. Mean ΔVE/ΔVCO2 showed no significant differences among the three groups (P = .503). Mean VEint discriminated significantly among the different groups (p 2 < 0.001). Ventilation efficiency index did not correlate either with LCI or Bhalla score. However, VE together with ΔVE/ΔVCO2 slope could predict Bhalla score (r 2 = 0.869, P = .006). No significant differences were found regarding ΔVE/ΔVCO2 slope levels between the three groups. Ventilation intercept (VEint ) was elevated significantly as disease progresses reflecting increased dead space ventilation. CF patients retain their ventilation efficiency to exercise even as lung function deteriorates by adopting a higher respiratory rate along with increased dead space ventilation.

Alternate gas washout indices: Assessment of ventilation inhomogeneity in mild to moderate pediatric cystic fibrosis lung disease

Normalized phase III slope (SnIII ) indices from multiple breath washout (MBW) estimate ventilation inhomogeneity. Alternate (*) protocols for SnIII indices exist, however the utility of these outcomes in children with mild-to-moderate cystic fibrosis (CF) is unknown. We measured nitrogen MBW and spirometry in 135 children (43 controls) aged 4-18 years. We assessed validity, practicability, and reliability of SnIII protocols. Outcomes included the ability to detect abnormal lung function, test agreement, measurement duration, intra-test repeatability, and quality. Lung clearance index (LCI) was abnormal in 80 (87%), Scond in 55 (60%), Scond* in 17 (19%), Sacin in 10 (11%), Sacin* in 11 (12%), and FEV1 in 28 (30%). Alternate protocols reduced measurement duration. Agreement of indices to detect abnormal lung function was poor. The quality of analysis and repeatability deteriorated with the alternate technique compared to standard. In children with mild-to-moderate CF lung disease, alternate protocols seem practical but clinimetric properties of standard SnIII protocols are preferable.

COMPARISON OF THE EFFECTIVENESS OF VISUAL IMAGERY TECHNIQUE AND PROGRESSIVE RELAXATION TECHNIQUE ON ANXIETY AND DEPRESSION IN SUBJECTS WITH MODERATE CHRONIC OBSTRUCTIVE PULMONARY DISEASE

Objectives: (1) To determine the effectiveness of visual imagery technique (VIT) on anxiety and depression in moderate chronic obstructive lung disease, (2) to determine the effectiveness of progressive relaxation technique (PRT) on anxiety and depression in moderate chronic obstructive lung disease (COPD), and (3) to compare the effectiveness of VIT and PRT on anxiety and depression in moderate COPD.Methods: Ethical clearance was obtained from the institutional ethical committee. A total of 45 stable moderate COPD patients were selected by simple random sampling, according to inclusion and exclusion criteria. 22 patients of Group A received VIT and 23 of Group B received PRT with a baseline treatment of conventional physiotherapy in both groups for 60 minutes twice a day for 5 days in the Pulmonology Department, Krishna Hospital, Karad.Result: Statistics was analyzed using paired t-test and unpaired t-test. In pre-intervention, there was no statistically significant difference seen for depression anxiety stress scale (DASS21) (p=D 0.0189, A 0.0002, S &lt;0.0001) (t=D 2.440, A 4.053, S 5.105), hospital anxiety depression scale (HADS) (p=D 0.7677, A 0.5121) (t=D 0.2973, A 0.6610), and 6-min walk test (6MWT) (p=D 0.5948, RPE 0.0658) (t=D 0.5359, RPE 1.888). On comparing, the post-interventional values between the two groups using unpaired t-test proved that there was extremely statistically significant difference seen for DASS21 (p=D 0.0011, A &lt;0.0001, S &lt;0.0001) (t=D 3.504, A 9.220, S 13.508), HADS (p=D &lt;0.0001, A &lt;0.0001) (t=D &lt;0.0001, A &lt;0.0001), and 6MWT (p=distance 0.7041, RPE &lt;0.0001) (t=distance 0.3824, RPE &lt;0.0001).Conclusion: VIT along with conventional physiotherapy was significant both statistically and clinically compared to PRT on anxiety and depression in moderate COPD patients.