Abstract
Objective
To assess whether self-reported acute mood or affect is associated with other patient-reported outcome measures, lung function, and all-cause mortality, in patients with fibrotic interstitial lung disease (f-ILD).
Patients and Methods
The Positive and Negative Affect Schedule (PANAS) is a 20-item questionnaire reflecting recent mood or affect over the past week, reported as Positive, Negative, or Ratio (Positive:Negative) subscores. Baseline and serial PANAS scores were assessed for their correlation with the Chronic Respiratory Questionnaire, Self-Management Assessment Scale 30, and lung function over a 3-year study period, and association with incident anxiety, depression, and all-cause mortality.
Results
In total, 199 patients with f-ILD were enrolled. Baseline PANAS scores correlated moderately with Chronic Respiratory Questionnaire and Self-Management Assessment Scale 30 scores. Higher PANAS Positive and Ratio scores were associated with higher percent predicted forced vital capacity. Mean PANAS scores were higher or lower when stratified by clinically suspected anxiety and/or depression and predictive of all-cause mortality on adjusted analysis, respectively. Incident anxiety and/or depression was not associated with worse survival outcome.
Conclusion
Self-reported acute mood or affect may be associated with RR-QoL, lung function, and adjusted all-cause mortality in patients with f-ILD.
Patients with fibrotic interstitial lung disease (f-ILD) and idiopathic pulmonary fibrosis (IPF) often experience impaired health-related quality of life (HR-QoL) owing to increasing or progressive symptom burden and frailty.1 Cough and dyspnea are common symptoms2 associated with decreased patient-reported well-being.3,4 Although specific treatments for f-ILD and IPF include oxygen support, immunosuppressive and antifibrotic medications, and pulmonary rehabilitation, most interventions do not result in sustained or improved quality of life. Obtaining a greater understanding of patient disease experience may provide for more holistic approaches to patient care and include aspects of HR-QoL as targeted outcomes.5
Patient-reported outcome measures (PROMs) are questionnaires or tools used to assess the direct and self-reported clinical experience of patients and, in f-ILD and IPF, have been shown to correlate with pulmonary function testing (PFT) and long-term survival.6,7 Patients with f-ILD and IPF may have increased rates of anxiety and depression with varied prevalences.8, 9, 10 It is unclear whether these findings reflect established or background disease compared with acute or situational responses to disease burden or progression. Assessments of immediate mood or affect may help delineate expected situational or transient emotional responses from developing or background clinical anxiety or depression, which warrant their own specific assessments and potential intervention.11
The Positive and Negative Affect Schedule (PANAS) is a 20-item association questionnaire used for assessing mood or affect with a momentary (immediate) or 1-week recall period, comprising 10 positive and 10 negative word items individually scored by the patient for relevance with a Likert scale. It has been internally validated, demonstrating stability over time,10 and studied previously in patients with heart failure12 and pulmonary sarcoid.13 As a measure of acute mood or affect, it has not been extensively studied in patients with f-ILD or IPF. We hypothesized that baseline and serial PANAS scores correlate with respiratory-related quality of life (RR-QoL), lung function, background anxiety and/or depression, and all-cause mortality.
Patients and Methods
Patient Selection and Study Design
This study is a post hoc analysis of a previously described prospective cohort of adult patients with f-ILD conducted over a 3-year period (institutional review board 17-005475).6 Briefly, patients were eligible if they were older than 18 years and had 10% or more fibrosis on chest computed tomography, with all f-ILD subtypes (IPF and non-IPF diagnoses) included. Collated baseline demographics included age, sex, and PFT (percent predicted forced vital capacity [FVC%] and percent predicted diffusion capacity for carbon monoxide [DLCO%]). Serial PROMs were completed at baseline and 3, 6, and 12 months from enrollment, with PFT measures obtained according to clinician preference. Protocolized PROM measures were associated with clinically obtained PFT measures if they occurred within 30 days (before or after) of each other. The modified Medical Research Council (mMRC) was obtained clinically at initial enrollment and used for comparing baseline dyspnea,14,15 with higher scores on a scale of 0 to 4 suggesting greater dyspnea. Patients were followed up during the study period up to 3 years for additional PFT assessments and vital status (last follow-up November 14, 2024). Clinically diagnosed or suspected anxiety and depression as documented in the medical record before, during the study period, and up to the date of last follow-up were collated retrospectively for this analysis. All-cause mortality was confirmed in the medical records.
PROMs
Three PROMs were obtained prospectively for the study, assessing positive and negative affect, RR-QoL, and self-management ability. These measures were completed at baseline (enrollment) and serially according to study protocol.6
Mood or Affect
The PANAS is a 20-item questionnaire with an immediate (in the moment) or 1-week recall period that assesses both positive and negative affect using 20 single-word items that highlighted either positive or negative connotations, individually scored on a 5-point Likert scale according to patient self-reported relevance.16 Total Positive and Negative scores range from 10 to 50 points for each and may be individually reported along with a ratio score (total Positive score over the total Negative score) representing overall positive mood or affect. Higher scores for all suggest comparatively greater positive or negative affect.17
Respiratory-Related Quality of Life
The Chronic Respiratory Questionnaire (CRQ) is a 20-item assessment of RR-QoL initially validated in patients with chronic obstructive pulmonary disease (COPD) and subsequently reported in patients with interstitial lung disease.18,19 Questions reflect 4 domains: Dyspnea, Fatigue, Emotion, and Mastery, with items under each domain scored on a 7-point Likert scale. Scores from the Dyspnea and Fatigue domains may be combined for a Physical Summary score, with Emotion and Mastery domains combined for an Emotional Summary score. The CRQ has previously been used to assess RR-QoL in patients with f-ILD.7,20,21
Self-management Ability
Self-management is defined as the ability to care for oneself as aging occurs, derived from previous theories of self-efficacy and self-care in older patients.22,23 The Self-Management Ability Scale (SMAS)-30 is a 30-item questionnaire highlighting 6 management skills: Taking Initiative, Self-efficacy, Investment Behavior, Positive Frame of Mind, Multifunctionality, and Variety. The SMAS-30 total score is the average of the other domains, with total mean and domain scores ranging from 0 to 100. Higher scores indicate better comparative self-management ability. The SMAS-30 has also been reported previously in patients with f-ILD.6,20,24
Statistical Analyses
Study data were collected and stored in REDCap (Research electronic Data Capture). Continuous data were presented as mean with SD or median with interquartile ranges, whereas categorical data were presented as counts and percentages. Baseline PROM scores were reported as mean ± SD. Patients were stratified by IPF versus non-IPF f-ILD with baseline comparisons made using χ2 test for categorical variables and 2-sample t-test for continuous variables. Mean PANAS scores were compared between those with and without anxiety and/or depression with a 2-sample t-test. Pearson correlation coefficients were used to assess the strength of PANAS correlations with other PROM and PFT parameters at baseline. A linear mixed-effects model for repeated measures was used to assess the association between PANAS scores and FVC% and DLCO%, adjusted for age, sex, diagnosis subtype (IPF vs non-IPF), and time on study in months. Individual subjects were considered random effects. Cox proportional hazards regression analysis was used to assess the association of baseline PANAS scores with all-cause mortality. Adjustments were made for a priori covariables of age, baseline FVC%, sex, and diagnosis type (IPF vs non-IPF). All analyses were completed without imputation for missing data, any variable with >10% missing were excluded from incorporation as an adjustment or predictor variable. Patients were followed up to date of last seen in the clinical visit in the medical record or death from any cause. Two-tailed P values of <.05 were considered statistically significant. Statistical analysis was performed using R (R Core Team [2024]; www.R-project.org/).
Results
Patient Characteristics
In total, 199 patients were enrolled over the 3-year study period, completing protocolized baseline and serial assessments. Sixty-five (33%) were diagnosed with IPF who were also older (72 vs 67 years; P<.001) and men (79% vs 48%; P<.001) (Table 1). There were no differences in baseline lung function. Dyspnea, as measured by the mMRC, appeared to be worse in those with non-IPF f-ILD (2.21 vs 1.84; P=.04). Concurrent anxiety and depression appeared more frequent in patients with non-IPF f-ILD (34% vs 13.9%; P=.002). All-cause mortality for those with IPF was 57% compared with 37% in non-IPF (P=.009).
Table 1.
Baseline Characteristics and PROM Scores Stratified by Disease Type
| Characteristic | IPF (n=65) | Non-IPF (n=134) | P |
|---|---|---|---|
| Age (y) | 72 ± 6.6 | 67 ± 9.9 | <.001 |
| Sex | <.001 | ||
| Male | 51 (79) | 64 (48) | |
| Female | 14 (21) | 70 (52) | |
| FVC% | 74.3 ± 21.8 | 69.8 ± 19.3 | .15 |
| DLCO% | 47.7 ± 15.4 | 50.9 ± 18 | .23 |
| mMRC | 1.84 ± 1.24 | 2.21 ± 1.11 | .04 |
| Anxiety | 6 (9.2) | 13 (9.7) | .92 |
| Depression | 9 (13.9) | 19 (14.2) | .95 |
| Both anxiety and depression | 9 (13.9) | 46 (34) | .002 |
| Status | .009 | ||
| Alive | 28 (43) | 84 (63) | |
| Dead | 37 (57) | 50 (37) | |
| PROM scores | |||
| PANAS positive | 32 ± 7.9 | 32.5 ± 8.1 | .73 |
| PANAS negative | 14.5 ± 5.6 | 16.9 ± 6.2 | .01 |
| PANAS ratio | 2.5 ± 1.1 | 2.2 ± 1.1 | .08 |
| CRQ dyspnea | 5.33 ± 1.51 | 4.84 ± 1.6 | .04 |
| CRQ fatigue | 4.37 ± 1.24 | 3.99 ± 1.31 | .06 |
| CRQ physical summary | 4.9 ± 1.26 | 4.46 ± 1.34 | .03 |
| CRQ mastery | 5.36 ± 1.28 | 4.99 ± 1.32 | .07 |
| CRQ emotions | 5.27 ± 1.19 | 4.87 ± 1.11 | .03 |
| CRQ emotional summary | 5.29 ± 1.15 | 4.92 ± 1.11 | .03 |
| SMAS-30 taking initiative | 71.7 ± 15.8 | 69.7 ± 16 | .41 |
| SMAS-30 behavior | 65.9 ± 18.4 | 64.6 ± 17.4 | .61 |
| SMAS-30 variety | 58.9 ±± 12.6 | 59.2 ± 13.7 | .89 |
| SMAS-30 multifunctionality | 77.1 ± 11.4 | 75.5 ± 11 | .34 |
| SMAS-30 self-efficacy | 89.7 ± 12.3 | 88.4 ± 12.7 | .51 |
| SMAS-30 positive frame of mind | 71.4 ± 18.9 | 69.9 ± 18.9 | .59 |
| SMAS-30 total | 72.5 ± 12 | 71.2 ± 12.4 | .50 |
Values are n (%) or mean ± SD.
CRQ, Chronic Respiratory Questionnaire; DLCO%, percent predicted diffusion capacity for carbon monoxide; FVC%, percent predicted forced vital capacity; mMRC, modified Medical Research Council; PANAS, Positive and Negative Affect Scale; PROM, patient-reported outcome measure; SMAS-30, Self-management Assessment Scale.
Baseline PANAS, CRQ, and SMAS-30 domain and total scores were compared between patients with and without IPF (Table 1). The PANAS Negative score was lower in patients with IPF (14.5 vs 16.9; P=.01), indicating less negative mood or affect. The CRQ Dyspnea (5.33 vs 4.84; P=.04), Physical Summary (4.9 vs 4.46; P=.03), and emotional domain (5.29 vs 4.92; P=.03) scores were higher in IPF, suggesting better comparative RR-QoL. There was no difference in self-management ability (SMAS-30 individual domain and total scores).
Pearson complete (2-variable unadjusted) correlation coefficients were calculated for baseline PANAS and PROM scores (Table 2). Weak correlations were seen with baseline PANAS scores and lung function (FVC% and DLCO%). Moderate positive and negative correlations were seen between PANAS scores and CRQ Physical and emotional summary scores, respectively, with the PANAS Ratio score having a strong positive correlation with the CRQ emotional summary score (0.718; P<.001). Finally, PANAS Positive and Ratio scores correlated moderately with all SMAS-30 domain and total scores.
Table 2.
Correlation of PANAS Scores With Clinical and PROM Findings
| Measurement | PANAS positive | PANAS negative | PANAS ratio |
|---|---|---|---|
| FVC% | 0.209 (.004) | −0.133 (.07) | 0.202 (.005) |
| DLCO% | 0.158 (.04) | −0.08 (.29) | 0.138 (.07) |
| CRQ physical summary | 0.498 (<.001) | −0.446 (<.001) | 0.546 (<.001) |
| CRQ emotional summary | 0.606 (<.001) | −0.659 (<.001) | 0.718 (<.001) |
| SMAS-30 taking initiative | 0.585 (<.001) | −0.313 (<.001) | 0.527 (<.001) |
| SMAS-30 behavior | 0.544 (<.001) | −0.377 (<.001) | 0.555 (<.001) |
| SMAS-30 variety | 0.523 (<.001) | −0.359 (<.001) | 0.529 (<.001) |
| SMAS-30 multifunctionality | 0.454 (<.001) | −0.305 (<.001) | 0.431 (<.001) |
| SMAS-30 self-efficacy | 0.505 (<.001) | −0.406 (<.001) | 0.493 (<.001) |
| SMAS-30 positive frame of mind | 0.509 (<.001) | −0.359 (<.001) | 0.508 (<.001) |
| SMAS-30 total | 0.639 (<.001) | −0.433 (<.001) | 0.625 (<.001) |
Values are correlation coefficient (P).
CRQ, Chronic Respiratory Questionnaire; DLCO%, percent predicted diffusion capacity for carbon monoxide; FVC%, percent predicted forced vital capacity; PANAS, Positive and Negative Affect Scale; PROM, patient-reported outcome measure; SMAS-30, Self-management Assessment Scale.
PANAS scores stratified by the presence or absence of clinically diagnosed anxiety and/or depression are presented in Table 3. Mean PANAS Positive and Ratio scores were lower in those with anxiety and/or depression, with higher negative scores.
Table 3.
Stratification of PANAS Scores by Incident Anxiety and/or Depression
| Measurement | Anxiety |
Depression |
Both |
||||||
|---|---|---|---|---|---|---|---|---|---|
| Present (MD) | Absent (MD) | 95% CIa | Present (MD) | Absent (MD) | 95% CIa | Present (MD) | Absent (MD) | 95% CIa | |
| PANAS positive | 29.5 | 33.9 | 1.99-6.9 | 26.9 | 34.2 | 2.03-6.6 | 28.6 | 33.7 | 2.37-7.87 |
| PANAS negative | 19.2 | 14.3 | −6.79 to −3.07 | 18.6 | 14.5 | −5.47 to −1.85 | 19.6 | 14.8 | −7.06 to −2.63 |
| PANAS ratio | 1.8 | 2.7 | 0.62-1.19 | 1.97 | 2.61 | 0.34-0.94 | 1.7 | 2.6 | 0.56-1.17 |
MD, mean difference; PANAS, Positive and Negative Affect Scale.
CIs were statistically significant (all P < .001).
A linear mixed-effects model was used to assess the linear relationship between PANAS scores and FVC% and DLCO%, adjusted for age, sex, diagnosis type, and months on study (Table 4). PANAS Positive (estimate, 0.16; 95% CI, 0.01-0.32; P=.04) and Ratio scores (estimate, 1.43; 95% CI, 1.15-2.72; P=.03) were associated with FVC%, whereas there was no association with DLCO%.
Table 4.
Association of PANAS Scores With Lung Function
| Estimate | 95% CI | P | |
|---|---|---|---|
| FVC% | |||
| PANAS positive | 0.16 | 0.01-0.32 | .04 |
| PANAS negative | −0.14 | −0.37 to 0.08 | .21 |
| PANAS ratio | 1.43 | 1.15-2.72 | .03 |
| DLCO% | |||
| PANAS positive | 0.04 | −0.14 to 0.21 | .67 |
| PANAS negative | −0.2 | −0.43 to 0.04 | .10 |
| PANAS ratio | 1.2 | −0.18 to 2.58 | .09 |
DLCO%, percent predicted diffusion capacity for carbon monoxide; FVC%, percent predicted forced vital capacity; PANAS, Positive and Negative Affect Scale.
Finally, univariable and multivariable Cox proportional regression analysis using baseline PANAS scores—for incident anxiety, depression, or both—as predictors of all-cause mortality are presented in Table 5. Baseline PANAS scores were not associated with increased all-cause mortality on univariable analysis, but after adjustment for a priori covariables of age, sex, FVC%, and diagnosis type, higher PANAS Negative (hazards ratio, 1.06; 95% CI, 1.02-1.10; P=.002) and lower PANAS Ratio scores (hazards ratio, 0.76; 95% CI, 0.61-0.95; P=.01) were associated. Incident anxiety, depression, or both was not associated with increased mortality.
Table 5.
Association of Baseline PANAS Scores and Incident Anxiety and Depression With All-Cause Mortality
| Measurement | Univariable HR | 95% CI | P | Multivariable HRa | 95% CI | P |
|---|---|---|---|---|---|---|
| PANAS positive | 0.99 | 0.96-1.01 | .4 | 0.98 | 0.96-1.01 | .30 |
| PANAS negative | 1.03 | 0.99-1.06 | .15 | 1.06 | 1.02-1.10 | .002 |
| PANAS ratio | 0.86 | 0.70-1.06 | .2 | 0.76 | 0.61-0.95 | .01 |
| Incident lone anxiety | 0.94 | 0.61-1.45 | .78 | 1.16 | 0.73-1.86 | .53 |
| Incident lone depression | 1.06 | 0.69-1.61 | .8 | 1.36 | 0.85-2.18 | .19 |
| Incident anxiety and depression | 0.88 | 0.54-1.43 | .61 | 1.09 | 0.63-1.85 | .76 |
FVC, forced vital capacity; HR, hazards ratio; IPF, idiopathic pulmonary fibrosis; PANAS, Positive and Negative Affect Scale.
Adjusted for age, sex, FVC, and diagnosis type (IPF vs non-IPF).
Discussion
Our study suggests that PANAS scores reflecting immediate mood or affect in patients with f-ILD may be associated with changes in RR-QoL, background anxiety and/or depression, lung function, and all-cause mortality. In this post hoc analysis, baseline and serial PANAS questionnaires were administered to 199 patients with f-ILD and stratified by IPF versus non-IPF diagnoses.6 Patients with IPF had lower PANAS negative scores, suggesting better mood or affect, whereas higher PANAS Positive and Ratio scores were associated with higher FVC% for the whole cohort. PANAS scores were also higher or lower when stratified by the presence of clinically suspected anxiety or depression, respectively, and were associated with increased all-cause mortality after covariable adjustment. Consequently, the PANAS questionnaire may not only serve as an assessment of acute mood or affect reflecting current disease burden but also have implications for progression and survival.
The PANAS has been studied in other chronic diseases for disease impact on patient mood or well-being. In patients with congestive heart failure, higher PANAS Positive scores were associated with lower inflammatory cytokine markers, although were not reflective of better self-care or improved disease management and prevention.12,25 Among patients with cancer, PANAS Positive and negative scores changed according to the phase of treatment and highlighted the need for a stepwise personalized approach to treatment plans.26, 27, 28 In patients with COPD, PANAS scores were associated with better self-management ability but not with PFT.29 Our study reports for the first time the association between acute mood or affect with severity of lung function, measures of RR-QoL, and all-cause mortality in patients with f-ILD.
Although we associated PANAS findings with clinical documentation of anxiety and depression, we were limited by the availability of nonprotocolized screening assessments and insufficient data for differentiating background versus new diagnoses. Anxiety and depression have been reported in patients with f-ILD, and our assessed prevalences appear to be in line with others.9, 10, 11,30 Lower HR-QoL has been associated with depression in patients with IPF, other idiopathic interstitial pneumonia, and autoimmune-associated interstitial disease.31,32 Dyspnea, as measured by mMRC, appears to predict both anxiety and depression in ILD.33 It remains unclear whether anxiety or depression are situational and transient after diagnosis or persist, given the chronic or progressive nature of f-ILD.34,35 Our study suggests PANAS scores delineating immediate mood or affect may be associated with potential background or developing anxiety and depression, but we cannot conclude whether PANAS reflects already existent disease or transient emotional responses to increased symptom burden or distress. PANAS scores also varied among newly diagnosed versus established cases without statistical significance and remained high even in those without clinically documented anxiety or depression. Interestingly, although PANAS negative and Ratio scores were associated with greater anxiety and/or depression, as well as all-cause mortality after covariable adjustment, anxiety and/or depression were not associated with increased mortality in our study, consistent with previous reporting.10 Clinical factors such as cough and dyspnea are known to contribute to greater anxiety and depression, with the latter reflecting diminished quality of life owing to disease burden or progression, rather than contributing independently to increased mortality.11
Our analysis found more negative mood or affect in patients with non-IPF f-ILD, coinciding with previously reported greater dyspnea and lower RR-QoL.6 This appears nonintuitive because IPF is often associated with greater disease progression and, even for this cohort, worse survival; however, patients without IPF reported more significant symptom burden, higher prevalence of clinically suspected anxiety and depression, and lower physical and emotional RR-QoL. Explanations for these findings are speculative but may reflect underlying disease or patient characteristics. For example, patients with IPF are often older and male and may be stereotypically associated with a demographic that is more stoic and accepting of expected disease progression or poorer outcomes.36 Self-reporting of comparatively better mood or affect may be seen in this group in contrast to younger patients who often lead more active lives or hold greater work or financial responsibilities.37 There is literature reflecting less disease impact in older patients or men with similar chronic disease burden.37, 38, 39, 40 Finally, implications of a more severe diagnosis may allow for better planning or management of expectations and attenuate uncertainty or anxiety regarding disease progression or outcome. The heterogeneity and uncertainty associated with unclear or overlapping diagnoses or nonstandardized management in non-IPF f-ILD may reasonably contribute to greater distress, particularly in nonresearch settings.41
Our study has several limitations. First, although this report is a post hoc analysis of a previously described prospective cohort,6 the PANAS questionnaire was implemented as part of the original study protocol and allowed for correlation with serial PFT and other PROMs. Correlation or association of PANAS with CRQ and SMAS-30 has been previously described in patients with COPD but not in those with f-ILD.29 Second, clinical assessments of anxiety and depression were obtained retrospectively and may be missing in terms of formal assessments or confirmation and timing with PANAS scores or other PROMs. We cannot, therefore, differentiate between PANAS scores reflecting known anxiety or depression versus potentially suggesting undiagnosed or developing disease. The impact of related treatments for known anxiety or depression, as well as the PANAS reflecting more immediate or acute mood or affect, may make this association more difficult to determine without a prospective assessment. Finally, our study involved a wide range of patients with f-ILD seen at a tertiary center presenting with varied disease severity and progression rates, perhaps limiting the applicability of our findings to other institutions or regional or demographic populations. We accounted for this by using a cross-sectional pragmatic population with broad inclusion criteria and preplanned adjustments for a priori covariables known to reflect differences in baseline disease severity or likelihood of progression.
Conclusion
Our findings suggest acute mood or affect may reflect disease burden in terms of association with other RR-QoL measures, lung function, and all-cause mortality, in a broad cohort of patients with IPF and non-IPF f-ILD. Further studies are needed to better understand the association of PANAS findings with other PROMs and undiagnosed background or developing anxiety and depression. It may also be helpful for delineating treatable mood or affect disorders from situational or transient emotional responses to initial diagnosis or changes in clinical lung disease burden.
Potential Competing Interests
The authors report no competing interests.
Ethics Statement
This is a retrospective post-hoc analysis of a previous prospective study (Mayo Clinic IRB 17-005475), without additional patient contact, therefore additional patient consent was not obtained.
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