Peterson, U.D.

Abstract Background Anxiety and depression have been reported in patients with fibrotic interstitial lung disease (f-ILD) and may be detected or evaluated with use of patient reported outcome measures (PROMs). The Generalized Anxiety Disorder-7 (GAD-7) is a screening tool for general anxiety, and the Patient Health Questionnaire (PHQ-9) is a screening tool for depression. We hypothesize that anxiety and depression in f-ILD may be independently associated with increased self-reported dyspnea and decreased physical activity. Methods This was a prospective observational cohort study conducted at a tertiary care institution. Patients with f-ILD were electronically sent PROMs to be completed at study enrollment, three months and six months. Patients also wore an activity monitor (ActiGraph) for 7 days at each time point. Included PROMs were the Modified Medical Research Council dyspnea scale (mMRC), GAD-7, and PHQ-9. The primary outcome was physical activity defined by average steps per day at each timepoint. Two sided, two sample t- tests were used to compare mean mMRC scores between participants with and without anxiety and depression. Mixed effects linear regression models with each patient as a random effect were used to evaluate the association between PROMS and physical activity. Models were adjusted for age, sex, FVC, and timepoint. Results Forty-eight patients were enrolled (mean age 69, female 46%, mean forced vital capacity (FVC%) 80%) and 45 completed baseline PROM and activity measures. In our cohort, 22 (46%) had background clinical anxiety and 17 (31%) had depression. In those with anxiety, 59% were classified as moderate and 2% as severe, while 47% were classified as moderate and 1% as severe in those with depression. Higher mMRC dyspnea scores were associated with both anxiety (1.955, p = 0.058) and depression (2.118, p = 0.022). Results from regression models indicated a one-point increase in GAD7, PHQ-9, and mMRC was associated with decrease in physical activity as defined by steps per day) ([GAD: -272 steps, p = 0.022], [PHQ-9: -188 steps, p = 0.014], [mMRC: -741 steps, p = 0.007]). Conclusions Patients with f-ILD and clinical anxiety and depression reported greater dyspnea and decreased measured physical activity. This abstract is funded by: None

Abstract Introduction Hydralazine is a common arterial vasodilator used in the treatment of hypertension and heart failure. Rarely, hydralazine can cause an overlapping syndrome of drug-induced lupus and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). The clinical spectrum of this disease process includes features of systemic lupus erythematous and AAV Case Presentation A 62-year-old male previous smoker with 50 pack-year history and hypertension presented with an eight-month history of exertional dyspnea and pleuritic chest pain. Prior to his presentation, he was treated for pneumonia with antibiotics without improvement. His subsequent chest imaging showed a right sided pleural effusion, evaluated by thoracentesis which was exudative and lymphocytic with negative cultures. He then developed progressive ground glass opacities, anemia, lymphopenia, splenomegaly, and acute kidney injury. With concern for underlying malignancy, he underwent a PET/CT and bone marrow biopsy which were not suggestive of malignancy. Serology revealed strongly a myeloperoxidase (MP) antibody (>8 U) with low titer proteinase-3 (PR3) antibody (1.2 U) and p-ANCA by immunofluorescence. Additional serology were notable for positive anti-double stranded DNA (dsDNA), positive ANA by hep2A, normal C3/C4, and creatinine peaking at 1.78 mg/dL, subnephrotic range proteinuria, and hematuria without RBC casts. Bronchoscopy noted progressively bloody return and 99% hemosiderin laden macrophages consistent with diffuse alveolar hemorrhage. Hydralazine was promptly discontinued with a clinical presentation consistent hydralazine-associated AAV and overlapping drug-induced lupus. They received remission induction therapy with IV methylprednisolone followed by tapering course of prednisone, rituximab, and avacopan. He was managed and monitored closely in the outpatient setting. With gradually improvement in renal function, a renal biopsy was deferred. Discussion Drug-induced lupus and drug-associated AAV can overlap in patients exposed to hydralazine, which can present up to several years after drug initiation. Renal and pulmonary involvement in hydralazine-induced lupus is uncommon and should prompt concern for drug-associated AAV. Compared with primary AAV, features suggestive of hydralazine-associated AAV include an adequate history of drug exposure and frequently a unique ANCA profile, hypocomplementemia, cytopenias, and additional seropositivity-including anti-histone and anti-dsDNA antibodies. Conclusion The cornerstone of management in hydralazine-induced lupus and hydralazine-associated AAV is early recognition and discontinuation of the offending medication. Induction of remission with standard immunosuppression is generally warranted, with specific therapies dictated by organ manifestations at diagnosis, similar to patients with primary AAV. Long-term outcomes in hydralazine-associated AAV appear comparable to those in primary AAV. The need for and duration of maintenance immunosuppression should be individualized based on patient presentation. This abstract is funded by: None

Abstract Rationale: Patients with fibrotic interstitial lung (f-ILD) disease often have decreased physical activity (PA) due to high symptom burden, with shortness of breath, cough, anxiety, and fatigue affecting health-related quality of life (HR-QOL). Previously undiagnosed anxiety and depression has been described in f-ILD though contributing factors remain unknown. We hypothesize that significant rates of disease-related anxiety and depression may be detected but not persist, representing situational or short-term responses to disease burden. We also hypothesize that real-world PA is an important contributor to or reflection of HR-QOL and associated with selected patient-reported outcome measures (PROMs). Methods: This was a single-center prospective observational cohort enrolling adult patients with established f-ILD. PROM questionnaires were sent electronically to patients at study enrollment and 3 months. These included the Modified Medical Research Council (mMRC), Fatigue Severity Scale (FSS), Generalized Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-9 (PHQ-9), Self-Management Ability Scale-30 (SMAS-30), and abbreviated Prolife of Mood States (POMS). PA was defined as mean number of steps per day over a 7-day period as measured by at-home Actigraphy, obtained at enrollment and 3 months (within 2 weeks of completing PROM questionnaires). Results: Forty five patients were included (mean age 69, female 49 %, non-IPF f-ILD 78%, mean forced vital capacity 77%). Baseline GAD-7 anxiety scores were ‘moderate’ in 45% and ‘severe’ in 5%. PHQ-9 depression scores were ‘moderately severe’ in 30% and ‘severe’ in 5%. Mean GAD-7 and PHQ scores were no different at baseline and three months (GAD7 10.18 vs 10, P = 0.653; PHQ-9 12.82 vs 13.32, P = 0.294). mMRC, FSS, and SMAS-30 scores were associated with daily step activity. A one-point increase in mMRC or FSS (greater dyspnea or fatigue) was associated with a decrease in daily steps of 1400 [CI: (-2000, -600), ] or 90 steps [CI: (-160, -15))], respectively. A one-point increase in SMAS-30 (greater self-management) was associated with an increase of 108 steps per day [CI: (25, 190-0.38) ]. Anxiety, depression, and mood did not appear to be associated with step activity GAD-7-4.5 (P = 0.982), PHQ-9-211.5 (P = 0.13), POMS -36.5 (P = 0.096). Conclusions: Clinical symptoms of anxiety and depression are prevalent in patients with f-ILD and do not appear diminished or improved in the short term. Dyspnea, fatigue, and self-management ability are associated with real-world measures of physical activity.

Abstract Rationale: Patients with fibrotic interstitial lung disease (F-ILD) often report high symptom burden with significant impact on their health-related quality of life. Self-reported disease experience may be unique or difficult to quantify yet have implications for functional and survival outcomes. We hypothesize that self-reported mood or affect may be associated with changes in lung function and predict mortality. Methods: This is a post-hoc analysis of a prospective cross-sectional study assessing changes in patient-reported outcome measures (PROM), lung function, and mortality incidence in patients with f-ILD. Serial measures of lung function and PROMs (baseline, 3, 6, and 12 months) were obtained over a 3-year period. The Positive and Negative Affect Scale (PANAS) is a 20-item questionnaire reflecting acute or immediate mood at the time of assessment, with higher scores for each domain highlighting greater positive or negative affect. A ratio of the Positive over the Negative score was used to summarize overall mood, with higher ratios reflecting more positive affect. PANAS scores at the time of lung function measures were assessed for their association with percent predicted forced vital capacity (FVC%) and diffusion capacity for carbon monoxide (DLCO%). Baseline PANAS scores were used to predict of all-cause mortality over the three-year study period. Results: One-hundred and eighty seven patients were included (mean age 69, female 37%, non-IPF f-ILD 67%). PANAS Negative scores were higher (16.9 vs 14.5, P = 0.01)with lower PANAS Ratio scores (2.5 vs 2.2, P = 0.08) in patients with non-IPF f-ILD, suggesting more negative affect or mood. A mixed effects model for repeated measures with each subject as a random effect found changes in the PANAS Positive score (point estimate 0.16, (0.01-0.32), P = 0.038) and Ratio score (1.43 (0.15-2.72), P = 0.029) were associated with changes in FVC% but not DLCO%. Baseline PANAS Negative (hazard ratios 1.06 (1.02-1.10), P = 0.002) and Ratio scores (HR 0.76 (0.61-0.95), P = 0.014) after adjusting for age, sex, FVC%, and diagnosis type (IPF vs non-IPF), were associated with increased all-cause mortality. Conclusions: Measured changes in self-reported mood or affect appear to be associated with changes in lung function and predict all-cause mortality. Direct assessments of patient disease experience may not only reflect symptom burden or disease progression but serve as targets of comprehensive management strategies or correlates of treatment efficacy given their potential association with lung function and survival.

This Inside Story describes the experiences of the authors, who both received cancer diagnoses during their fellowships.