Breathlessness catastrophizing relates to poorer quality of life in adults with cystic fibrosis

JCF-01697; No of Pages 8

Journal of Cystic Fibrosis xx (2018) xxx – xxx www.elsevier.com/locate/jcf

Original Article

Breathlessness catastrophizing relates to poorer quality of life in adults with cystic fibrosis☆ Danijela Maras a,b,⁎, Louise Balfour a,b,c,d , Giorgio A. Tasca a,b,d , Ena Gaudet b , Shawn D. Aaron b,d,e , William D. Cameron b,d,e , Smita Pakhale b,d,e a

School of Psychology, University of Ottawa, Canada b The Ottawa Hospital Research Institute, Canada c Psychology, The Ottawa Hospital, Canada d Faculty of Medicine, University of Ottawa, Canada e Respirology, The Ottawa Hospital, Canada

Received 8 June 2018; revised 11 August 2018; accepted 13 August 2018 Available online xxxx

Abstract Background: Cystic Fibrosis (CF) is the most common genetic disease affecting children and young adults in Canada. It is a multi-system disease, however lung disease is largely responsible for mortality. Treatment advances have resulted in increased life expectancy and a subsequent need to better understand psychosocial issues associated with quality of life in adults living with CF. Emerging research suggests that anxiety and depression are related to poorer health-related quality of life (HRQoL) in CF patients, but there is little research examining cognitive processes, such as breathlessness catastrophizing. The present study addresses this gap in the literature. Methods: Participants in this study are based on a convenience sample of patients recruited during their regular CF clinic appointments at a tertiary care center. Forty-five adults (Mage = 30.73 years) completed measures of lung function, depression, anxiety, pain, breathlessness catastrophizing, and HRQoL at one time point. Results: Results of a hierarchical multiple regression indicate that increased breathlessness catastrophizing was related to poorer HRQoL, after controlling for lung function, depression, anxiety, and pain (p b .05). Depression, pain, and breathlessness catastrophizing all emerged as significant unique predictors of HRQoL. Conclusions: Breathlessness catastrophizing is a potential target for clinical intervention and might impact HRQoL. Further research on breathlessness catastrophizing in CF is warranted including longitudinal studies to examine the mechanisms by which breathlessness catastrophizing relates to HRQoL and treatment outcomes in CF. © 2018 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved. Keywords: Anxiety; Breathlessness Catastrophizing; Cystic Fibrosis; Depression; Quality of Life

1. Introduction Cystic fibrosis (CF) is an autosomal recessive genetic disease, and is the most common genetic disease affecting children and young adults of Northern European descent. It is a ☆ Previous presentation: Presented in poster format at the Canadian Psychological Association's 78th Annual Convention in Toronto, Canada in June 2017 ⁎ Corresponding author at: University of Ottawa, Department of Psychology, 136 Jean-Jacques Lussier Private Ottawa, Ontario K1N 6N5, Canada. E-mail address: [email protected] (D. Maras).

multi-system disease, however lung disease is largely responsible for mortality. Although CF is a life-limiting and incurable condition, advances in its treatment have resulted in most people surviving into adulthood. The median life expectancy is 51.8 years in Canada, 47.1 in the United Kingdom, and 41.1 in the United States [1]. As the median survival for individuals with CF continues to improve, understanding psychosocial issues and optimizing health-related quality of life (HRQoL) becomes increasingly important [2–4]. HRQoL is multi-dimensional and includes a person's subjective evaluation of his or her own functioning in

https://doi.org/10.1016/j.jcf.2018.08.008 1569-1993© 2018 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved. Please cite this article as: Maras D, et al, Breathlessness catastrophizing relates to poorer quality of life in adults with cystic fibrosis, J Cyst Fibros (2018), https://doi.org/ 10.1016/j.jcf.2018.08.008

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D. Maras et al. / Journal of Cystic Fibrosis xx (2018) xxx–xxx

the context of their disease status, treatment interventions, and impact these have on their daily lives [5]. Pulmonary exacerbations and lung function are related to poorer HRQoL in longitudinal studies of people with CF [6,7]. Pain is a common symptom and clinical complication in CF; approximately 89% of adults living with CF experience pain [8]. Although pain is not associated with disease severity in adults with CF, it is associated with poorer HRQoL and increased symptoms of anxiety, depression, and pain catastrophizing [9]. The psychological burden of CF is high [2]. Approximately 19% and 32% of individuals with CF experience depression and anxiety, respectively [10]. Depression and anxiety are associated with negative sequelae in CF such as poorer pulmonary function, more severe chest symptoms, reduced physical functioning, increased hospitalization and healthcare costs, higher rates of missed appointments, poorer adherence to treatment, and higher rates of tobacco smoking, drinking, and drug use [10–13]. In longitudinal studies, depression and anxiety are also associated with decreases in lung function in CF [14,15]. In cross-sectional samples, depression and anxiety are related to poorer HRQoL among CF patients [12], even after controlling for lung function [16–18]. As a result of The International Committee on Mental Health in CF's recommendations on screening and treating depression and anxiety, there has been an increased research interest in understanding these psychological symptoms [19]. Individuals with CF also acknowledge the importance of being screened and treated for psychological symptoms [20,21]. This highlights the importance of screening CF patients for psychological symptoms, and exploring other psychological factors related to HRQoL. Breathlessness catastrophizing (BC) is one such cognitive style that warrants exploration in CF. Breathlessness is very common (64% to 77%) among people living with CF [2] and negatively impacts HRQoL, even when pulmonary function is within the mildly affected to normal range [22]. Catastrophizing is defined as an exaggerated negative cognitive-emotional orientation toward actual or anticipated noxious stimuli [23]. This includes the negative affect constructs of rumination, magnification, and feelings of hopelessness about the noxious stimuli [23]. These constructs overlap with anxiety and depression, and there has been some debate about whether or not catastrophizing is a distinct construct [24]. Research on the association between anxiety and CF outcomes has measured anxiety in the broad sense. Studies on pain [25], asthma [26], and chronic obstructive pulmonary disease (COPD) [27] that examined specific fear-related measures (e.g., Pain Catastrophizing Scale, Catastrophizing about Asthma Scale, Breathlessness Beliefs Questionnaire) found that specific fear measures are more robust predictors of outcomes, above and beyond global anxiety measures. Catastrophizing is well-documented in the pain literature and is one of the strongest psychological predictors of pain and negative health outcomes [25]. In fact, pain and breathlessness perceptions are processed in similar brain areas [28]. There has been a movement in the respiratory literature (i.e., COPD) to examine the cognitive process of BC and how it relates to

illness severity and treatment outcomes [29–32]. Given that breathlessness is a core symptom of CF that causes impairment in functioning [22], and that specific fear measures relate to outcomes in other medical conditions, understanding the relationship between BC and HRQoL in CF is warranted. 2. Objective and hypothesis Despite the experience of breathlessness being so prevalent and burdensome among those living with CF,BC and its relationship to HRQoL in CF has not been studied. The present study is the first to address this gap in knowledge by examining if BC is associated with HRQoL in a sample of adults living with CF. It was hypothesized that increased BC would be significantly associated with poorer HRQoL, above and beyond lung function, pain, depression, and anxiety. 3. Methods 3.1. Participants A total of 52 adults with CF were consecutively approached to participate in this study. Of the 49 (94%) who enrolled, four participants (8%) did not return their completed questionnaires, resulting in a final sample of 45 adults. 3.2. Procedure This study is part of a pilot project entitled “The Ottawa Cystic Fibrosis Treatment Knowledge and Adherence Program” that included a small observational cohort study at a multidisciplinary adult CF outpatient clinic at a tertiary care center in Ottawa, Canada. Participants were recruited during a regularly scheduled CF clinic appointment from May 2011 to June 2013. Inclusion criteria were: 1) English-speaking adults (≥ 18 years); 2) Expected to continue receiving care at the CF clinic for 1 year; 3) Able and willing to give informed consent. Exclusion criteria were: 1) Expected survival of less than one year; 2) Lung transplant recipient. At the time of this cohort study, the CF outpatient clinic served approximately 105 to 123 patients. Using a consecutive sampling approach, patients meeting inclusion criteria were invited to participate until the required sample size was achieved. Participants completed selfreport questionnaires and provided consent to access data in their medical charts. The Ottawa Hospital's research ethics board approved the study and consenting participants were offered $15.00 CAD to cover transportation costs. 3.3. Measures 3.3.1. Socio-demographics Variables such as age, biological sex, ethnicity, level of education, and employment status were collected. 3.3.2. Lung function Lung function was assessed at the clinic visit using the percentage of normal forced expiratory volume at 1 s (FEV1%)

Please cite this article as: Maras D, et al, Breathlessness catastrophizing relates to poorer quality of life in adults with cystic fibrosis, J Cyst Fibros (2018), https://doi.org/ 10.1016/j.jcf.2018.08.008

D. Maras et al. / Journal of Cystic Fibrosis xx (2018) xxx–xxx

[33]. Mild disease was defined as FEV1 N 70% of predicted, moderate disease as FEV1 = 40–70%, and severe disease as FEV1 b 40% [34]. 3.3.3. Depression The Center for Epidemiologic Studies Depression Scale (CES-D) is a psychometrically sound 20-itemself-report scale assessing symptoms of depression [35,36]. Items are rated on a 4-point Likert scale (0 = rarely or none of the time to 3 = most or all of the time). Total scores range from 0 to 60, with higher scores indicating greater depressive symptomatology [35]. Scores ≥16 indicate clinical levels of depressive symptoms [35]. In the present study, internal consistency of the CES-D is high, with α = 0.90. 3.3.4. Anxiety The 7-item Generalized Anxiety Disorder scale (GAD-7) was used to assess symptoms of anxiety [37]. The GAD-7 yields a total score, ranging from 0 to 21, with higher scores indicating greater symptoms of anxiety. Each item is rated on a 4-point Likert scale (0 = not at all to 3 = nearly every day). Total scores between 0 and 4 are indicative of minimal anxiety, between 5 and 9 mild, 10–14 moderate, and 15–21 severe [37]. The GAD-7 has adequate psychometric properties [37]. In the present study, internal consistency of the GAD-7 is high, with α = 0.88. 3.3.5. Pain Pain was assessed using the 4 item pain subscale of the Cystic Fibrosis Symptom Scale (CFSS), which was developed by the researchers for the purposes of the present study. The CFSS is a 41-item questionnaire that assesses the frequency of pain symptoms in the past 7 days. Each item is rated on a 5point Likert scale (0 = not at all to 4 = all the time). The pain subscale score ranges from 0 to 16, with higher scores indicating more pain symptoms. Internal consistency of the pain subscale in the present study is good, with α = 0.73. 3.3.6. Breathlessness catastrophizing The Breathlessness Catastrophizing Scale (BCS) is a reliable and valid 13-item questionnaire that measures thoughts and feelings associated with experiences of breathlessness [31]. Adapted from the validated Pain Catastrophizing Scale [23], the BCS has been validated in a sample of adults with COPD [31], and has been used in outcomes research in COPD [31,32]. An fMRI study demonstrated a significant correlation between BCS scores and the anticipation of breathlessness in healthy volunteers, adding to the validity of the scale [38]. Each item is rated on a 5-point Likert scale (0 = not at all to 4 = all the time). The BCS yields a total score ranging from 0 to 52, with higher scores indicating more catastrophizing. Internal consistency of the BCS in the present CF sample is high, with α = 0.94. 3.3.7. Health-related quality of life HRQoL was assessed using the reliable and valid Cystic Fibrosis Quality of Life (CFQoL) questionnaire [39]. This 52item questionnaire measures QoL across 9 domains of physical

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and mental health functioning specific to people living with CF. Each item is rated on a 6-point Likert scale (1 = all of the time/ strongly agree to 6 = never/strongly disagree). The total score was used in the present study. Scores on the CFQoL are transformed so that values are between 0 and 100. High total scores are indicative of higher perceived HRQoL. Internal consistency of the CFQoL total score is high in the present study, with α = 0.95. 3.4. Data analysis and screening A hierarchical multiple regression analysis was used to examine the contribution of lung function (step 1); pain, depression, anxiety (step 2); and BC (step 3) to HRQoL. The Statistical Package for the Social Sciences (SPSS) 23.0 with an alpha level of p b .05 was used for all analyses. Given the novelty of the present study and the small sample size, analyses were conducted without the addition of socio-demographic covariates. Data were screened using recommended procedures [40]. There were no missing data for FEV1%, depression, pain, or BC. The percent of missing data for anxiety and HRQoL were 2.2% and 11.1%, respectively. Little's MCAR test was not significant, χ2 (914) = 0.000, p = 1.00, indicating that data were missing completely at random. Expectation maximization was used to impute missing data [41]. One univariate outlier was identified for pain; it was adjusted to within z = 3.29. No multivariate outliers were identified. The depression, anxiety, and pain variables were positively skewed, so analyses were run with and without transformations; because results did not differ, and for ease of interpretation, the non-transformed results are presented here. There were no issues with singularity or multicollinearity. 4. Results 4.1. Sample characteristics Descriptive statistics and frequencies are presented in Table 1. The sample consisted of mostly White, well-educated, and employed adults. Fifty-seven percent (n = 26) of the sample was male. Mean FEV1 was approximately 53% of predicted, indicative of a moderately ill sample with CF [34]. Forty percent of the sample (n = 18) had clinically elevated levels of depression, and 13.3% (n = 6) had moderate levels of anxiety. 4.2. Correlations Bivariate correlations are presented in Table 2. HRQoL was significantly and negatively correlated with depression, anxiety, pain, and BC. BC was significantly positively correlated with sex, depression, anxiety, and pain; significantly negatively correlated with age; and not correlated with lung function. 4.3. Breathlessness catastrophizing scale Given that this is the first study to use the BCS [31] in a sample of adults with CF, we wish to provide readers with

Please cite this article as: Maras D, et al, Breathlessness catastrophizing relates to poorer quality of life in adults with cystic fibrosis, J Cyst Fibros (2018), https://doi.org/ 10.1016/j.jcf.2018.08.008

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4 Table 1 Descriptive Characteristics of the Sample. Indicator

Age (years) FEV1% Depression Anxiety Pain Breathlessness catastrophizing CFQoL

Ethnicity White-Caucasian Other Education High school Some college/university University degree obtained Postgraduate degree (e.g., MA, PhD) Employment status Working part-time, full-time, or full-time student Currently not working (e.g., sick leave, retired) Other Disease severity Mild (FEV1% N 70%) Moderate (FEV1% = 40%–70%) Severe (FEV1% b 40%) Anxiety None (≤4) Mild (≥5 and b10) Moderate (≥10 and b15) Severe (≥15) Depression Normative (b16) Clinical range (≥16)

Male (n = 26)

Female (n = 19)

Total (N = 45)

M (SD)

M (SD)

M (SD)

32.77 (9.48) 53.58 (21.54) 11.38 (7.93) 3.39 (3.92) 2.15 (2.38) 11.27 (11.16) 77.70 (12.54) Male (n = 26) n (%)

27.95 (12.09) 51.63 (16.28) 16.47 (11.89) 4.37 (3.58) 3.11 (2.77) 18.84 (13.20) 74.26 (13.79) Female (n = 19) n (%)

30.73 (10.80) 52.76 (19.31) 13.53 (10.00) 3.80 (3.77) 2.56 (2.56) 14.47 (12.50) 76.24 (13.04) Total (N = 45) n (%)

25 (96.2) 1 (3.8)

17 (89.5) 2 (10.5)

42 (93.3) 3 (6.7)

7 (26.9) 4 (15.4) 12 (46.2) 3 (11.5)

2 (10.5) 6 (31.6) 11 (57.9) 0 (0)

9 (20.0) 10 (22.2) 23 (51.1) 3 (6.7)

19 (73.1) 4 (15.4) 3 (11.5)

11 (57.9) 8 (42.1) 0 (0)

30 (66.7) 12 (26.7) 3 (6.7)

8 (30.8) 9 (34.6) 9 (34.6)

4 (21.1) 12 (63.2) 3 (15.8)

12 (26.7) 22 (48.9) 11 (24.4)

19 (73.1) 4 (15.4) 3 (11.5) 0 (0)

10 (52.6) 6 (31.6) 3 (15.8) 0 (0)

29 (64.4) 10 (22.2) 6 (13.3) 0 (0)

18 (69.2) 8 (30.8)

9 (47.4) 10 (52.6)

27 (60.0) 18 (40.0)

Note. Descriptive statistics are calculated after imputing missing data. CFQoL = Cystic fibrosis-related quality of life; FEV1% = Percent predicted of normal forced expiratory volume at 1 s.

some additional psychometric data. The mean, standard deviation, and item-total correlation for each of the 13 items is presented in Table 3. None of the item-level correlations were negative, indicating that all items contributed to the scale and were cohesive. With a Cronbach's alpha of 0.94 and an average inter-item correlation of 0.72, the BCS demonstrates excellent internal consistency in this CF sample.

6.4% of the variation in HRQoL, ΔR2 = 0.064, F [1, 39] = 5.88, p = 0.02, for a total of 57.4% of variance explained, F [5, 39] = 10.51, p b 0.001, R2 = 0.57. In this model, depression (pr = −0.327, p = 0.037), pain (pr = −0.338, p = 0.03), and BC (pr = −0.362, p = 0.02) were significant unique predictors of HRQoL. 5. Discussion

4.4. Psychological variables associated with health-related quality of life Results of the hierarchical multiple regression (Table 4) reveal that in step 1, FEV1% did not significantly account for variance in HRQoL, F [1, 43] = 3.22, p = 0.08, R2 = 0.07. Adding depression, anxiety, and pain in step 2 significantly explained an additional 44% of the variance in HRQoL, and this change in R2 was significant, F [3, 40] = 11.97, p b 0.001. Depression (pr = −0.358, p = 0.02) and pain (pr = −0.382, p = 0.013) were significant unique predictors in the model. Including BC in step 3 significantly explained an additional

This study examined psychological variables and HRQoL in a sample of adults living with CF. Researchers have begun to recognize the importance of assessing depression, anxiety, and HRQoL among adults with CF [6,10,12,19,42]; however, there is a dearth of research examining BC. The present study contributes to the literature by providing a first look at BC among adults living with CF. Forty percent of the present sample reported clinically significant levels of depression (i.e., CES-D scores ≥16), which is higher than the 19% reported in a large multicenter study [10]. Approximately 13% of the present sample reported

Please cite this article as: Maras D, et al, Breathlessness catastrophizing relates to poorer quality of life in adults with cystic fibrosis, J Cyst Fibros (2018), https://doi.org/ 10.1016/j.jcf.2018.08.008

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Table 2 Correlations and p-Values of Baseline Variables. 1. Age 1. Age 2. Sex 3. FEV1% 4. Depression 5. Anxiety 6. Pain 7. BC 8. CFQoL

– −0.223 (0.141) 0.018 (0.907) −0.227 (0.133) −0.150 (0.325) 0.015 (0.920) −0.393 (0.008) 0.183 (0.229)

3. FEV1%

2. Sex

4. Dep

5. Anx

6. Pain

7. BC

– −0.050 (0.743) 0.254 (0.092) 0.129 (0.397) 0.185 (0.223) 0.303 (0.043) −0.132 (0.388)

– 0.046 (0.762) 0.204 (0.178) −0.160 (0.293) −0.186 (0.222) 0.264 (0.080)

– 0.745 (b0.001) 0.454 (0.002) 0.433 (0.003) −0.580 (b0.001)

– 0.406 (0.006) 0.389 (0.008) −0.428 (0.003)

– 0.401 (0.006) −0.575 (b0.001)

– −0.585 (b0.001)

Note. N = 45. Anx = Anxiety; BC = Breathlessness catastrophizing; CFQoL = Cystic fibrosis-related quality of life; Dep = Depression; FEV1% = Percent predicted of normal forced expiratory volume at 1 s. Sex: male = 0 and female = 1. Significant correlations are bolded.

a moderate level of anxiety, compared to 32% in the Quittner et al. study [10]. Given the absence of normative values for the BCS, comparing mean scores in the present sample to previously published research may be helpful. Mean BC in the present sample of CF patients was 14.5 (SD = 12.5), which is similar to a sample of patients with COPD who were former smokers [13.0 (SD = 10.97)] [29]. Mean BC in our sample is lower than mean BC scores reported in two published studies of COPD patients: 18.1 (SD = 11.8) in the BCS validation paper [31], and 26.4 (SD = 13.4) and 22.0 (SD = 11.6) in an intervention and control group, respectively, in a randomized controlled trial [32]. Differences in sample characteristics such as disease type (CF versus COPD), FEV1% [52.8 (SD = 19.3) Table 3 Item-level Analysis of the Breathlessness Catastrophizing Scale in a Sample of Adults with Cystic Fibrosis. Breathlessness Catastrophizing Scale Items

M

1.

1.02 1.18 0.695

2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13.

I worry all the time about whether the breathlessness will subside. I feel I can't go on. It's terrible and I think it's never going to get any better. It's awful and I feel that it overwhelms me. I feel I can't stand it anymore. I become afraid that the breathlessness will get worse. I keep thinking of other times I have been breathless. I anxiously want the breathlessness to go away. I can't seem to keep it out of my mind. I keep thinking about how out of breath I am. I keep thinking about how badly I want the breathlessness to stop. There's nothing I can do to reduce the intensity of the breathlessness. I wonder whether something serious might happen.

SD

Item-total correlation

1.09 1.16 0.466 0.89 1.05 0.711 1.04 1.22 0.849 1.04 1.30 0.729 1.38 1.34 0.802 0.82 1.07 0.597 1.53 1.41 0.667 0.87 1.24 0.819 1.07 1.23 0.822 1.24 1.43 0.810 1.16 1.26 0.700 1.31 1.36 0.708

Note. See Solomon et al. [31] for Breathlessness Catastrophizing Scale.

versus 41.0 (SD = 19.5) and 37.7 (SD = 11.8), respectively], and age [30.7 (SD = 10.1) versus 66.1 (SD = 11.2) and 67.2 (SD = 7.7), respectively] may explain these differences in BC scores [31,32]. In fact, the present CF sample has significantly higher FEV1%1 and is significantly younger2 than both COPD samples [31,32]. Although examining sex differences was not a primary goal of the present study, there was a trend of females reporting more symptoms of depression, anxiety, pain, and BC. In the pain literature, some studies have found that females catastrophize more, whereas other studies have found that males catastrophize more [24]. The bivariate correlations are in the expected direction. Similar to findings by Solomon and colleagues in a COPD sample [31], BC was significantly positively correlated with clinical measures of depression and anxiety, but not significantly correlated with FEV1%. However, Solomon and colleagues [31] found a significant correlation between BC and a different measure of lung function (i.e., forced vital capacity: FVC). Although an equivalent measure to lung function does not exist in the pain literature, pain catastrophizing has been associated with physical disability among various pain conditions [43]. BC was also significantly negatively correlated with age (younger adults tend to catastrophize more than older adults), and positively correlated with sex (females tend to catastrophize more than males). Despite these significant correlations, neither age nor sex emerged as significant predictors of HRQoL in a post-hoc simplified regression model (data not shown; step 1: age, sex; step 2: depression, pain; and step 3: BC). Moreover, neither an age*BC nor a sex*BC interaction significantly predicted HRQoL in separate post-hoc regression models (data not shown). Previous literature has not explored age and sex 1 Difference between FEV1% of present sample and: 1) Solomon and colleagues: t (285) = −3.72, p b .0001; 2) Farver-Vestergaard and colleagues: t (127) = −5.487, p b .0001. 2 Difference between mean age of the present sample and: 1) Solomon and colleagues: t (285) = 19.56, p b .0001; 2) Farver-Vestergaard and colleagues: t (127) = 22.13, p b .0001.

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Table 4 Hierarchical Multiple Regression Analysis Predicting Cystic Fibrosis Quality of Life from Forced Expiratory Volume, Depression, Anxiety, Pain, and Breathlessness Catastrophizing.

Step 1 FEV1% Step 2 FEV1% Depression Anxiety Pain Step 3 FEV1% Depression Anxiety Pain BC

B

SE

t

p

pr

0.18

0.10

1.79

0.080

0.264

0.16 −0.54 −0.10 −1.71

0.08 0.22 0.60 0.66

1.99 −2.43 −0.16 −2.61

0.053 0.020 0.872 0.013

0.300 −0.358 −0.026 −0.575

0.12 −0.46 0.11 −1.42 −0.31

0.08 0.21 0.58 0.63 0.13

1.52 −2.16 0.18 −2.25 −2.43

0.136 0.037 0.855 0.030 0.020

0.237 −0.327 0.029 −0.338 −0.362

R

R2

ΔR2

p change

0.264

0.070

0.070

0.080

0.714

0.510

0.440

b0.001

0.758

0.574

0.064

0.020

Note. N = 45. SE = standard error of B; CI = Confidence interval; FEV1% = Percent predicted of normal forced expiratory volume at 1 s; BC = Breathlessness catastrophizing.

differences in BC. Our preliminary study is not powered to examine how age, sex, and other diversity variables relate to BC in CF. Future research with larger and more diverse samples should examine these relationships. The BCS showed excellent internal consistency in this small sample of CF patients. The psychometric properties of the BCS should be examined in a larger and more diverse sample to contribute to BCS validation in CF. Results from this study suggest that depression, pain, and BC, but not anxiety or lung function, each significantly contribute to poorer HRQoL in patients with CF. Given the large correlation between BC and HRQoL, and the conceptual overlap between BC, depression, and anxiety, BC was included in the regression model in the last step to examine if BC contributed unique variance to HRQoL. Indeed, BC contributed unique variance to HRQoL, above and beyond lung function, pain, depression, and anxiety. This lends support to BC as distinct from the related constructs of depression and anxiety. Findings have potential implications for interdisciplinary clinical intervention in CF care, rehabilitation, and overall improvement of HRQoL. Building on previous COPD research [27,31,32], our findings introduce BC as a potential modifiable treatment target in CF warranting further exploration. If future research supports BC as a clinically relevant treatment target, a mindfulness-based cognitive therapy intervention delivered in the context of a multi-disciplinary rehabilitation program may help decrease BC in CF, which may in turn improve HRQoL. Mindfulness-based cognitive therapy has demonstrated preliminary success in decreasing BC in COPD patients [32]. Mindfulness interventions are also useful in improving pain [44] and depression [45], and therefore might be well-suited to help improve HRQoL in CF patients by simultaneously targeting BC, pain, and depression. BC may be a barrier to CF treatment uptake and adherence, and is therefore important to assess and treat. Given that physical exercise training, a key component of CF treatment [46,47], can induce feelings of breathlessness, it is understandable that adherence to exercise regimens can be challenging, particularly for those with CF who might catastrophize about

breathlessness. Even activities of daily living, such as walking or climbing stairs, might be avoided for fear of provoking breathlessness. Unfortunately, avoiding physical activities that can trigger breathlessness may contribute to the progression of respiratory disease, a poorer prognosis [47], a diminished repertoire of social activities, and ultimately poorer HRQoL. The first, and possibly the largest, limitation of this study is the cross-sectional design, which does not allow for causal inferences. It is possible that other factors not assessed in the present study contribute to poorer HRQoL in CF. For example, patients with COPD and comorbid panic disorder report higher levels of breathlessness in response to respiratory loads [48]. Although anxiety was accounted for in the present study, future research could assess symptoms of panic disorder. Another limitation is the small and relatively homogeneous sample; however, this novel study and its findings contribute to the literature and can inform future research, which should include a larger and more diverse sample. Strengths of the present study include the use of reliable and valid psychometric measures with very high reliability in the present sample, objectively measured clinical lung function, and a first introduction to BC as a potential intervention target in CF. The present study adds to the extant CF literature by demonstrating that depression, pain, and BC are significant unique predictors of poorer HRQoL. Findings emphasize the importance of assessing psychological functioning in adults living with CF, and highlight the added value of assessing the cognitive process of BC in this population. Similar to pain catastrophizing, BC may undermine response to treatment and maintenance of treatment gains [49], suggesting that more research on this topic is warranted. Findings have implications for CF treatment and care, and also for other populations that experience breathlessness (e.g., respiratory disease, asthma, cardiac conditions, cancer, neuromuscular conditions, and palliative care). Although more research is needed, the present findings introduce BC as a putative marker of poorer HRQoL in CF, above and beyond the clinical measure of lung function, pain, and more traditionally assessed psychological variables of depression and anxiety.

Please cite this article as: Maras D, et al, Breathlessness catastrophizing relates to poorer quality of life in adults with cystic fibrosis, J Cyst Fibros (2018), https://doi.org/ 10.1016/j.jcf.2018.08.008

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Increasing our understanding of factors related to HRQoL in CF can help improve treatment and rehabilitation efforts, which may ultimately improve the overall health and well-being of individuals living with CF. Authors' contributions DM, LB, GT, SA, WC, and SP are responsible for study concept and study design. EG was responsible for data collection and data entry. DM was responsible for data cleaning and data analysis for this study. DM, LB, and SP were involved in drafting the manuscript. All authors made substantial contribution to the interpretation of the data, revised the article critically, and gave their final approval of the manuscript. Conflict of interest statement The authors (DM, LB, GT, EG, SA, WC, and SP) declare that they have no competing interests. Acknowledgements Thank you to those who participated in the study. This research was supported by a grant from The Department of Medicine, Ottawa, Canada, and investigator initiated research funding from Novartis, Ltd., Canada. Study design, data collection, and analysis were done independently of funding sources. References [1] Salvatore D, Buzzetti R, Mastella G. Update of literature from cystic fibrosis registries 2012–2015. Part 6: epidemiology, nutrition and complications. Pediatr Pulmonol 2017;52(3):390–8. [2] Sawicki GS, Sellers DE, Robinson WM. Self-reported physical and psychological symptom burden in adults with cystic fibrosis. J Pain Symptom Manage 2008;35(4):372–80. [3] Salek MS, Jones S, Rezaie M, Davies C, Mills R, Ketchell RI. Do patientreported outcomes have a role in the management of patients with cystic fibrosis? Front Pharmacol 2012;3(38):1–8. [4] Elborn JS, Bell SC, Madge SL, Burgel P-R, Castellani C, Conway S, et al. Report of the European Respiratory Society/European Cystic Fibrosis Society task force on the care of adults with cystic fibrosis. Eur Respir J 2016;47(2):420–8. [5] Gee L, Abbott J, Hart A, Conway SP, Etherington C, Webb AK. Associations between clinical variables and quality of life in adults with cystic fibrosis. J Cyst Fibros 2005;4(1):59–66. [6] Habib AR, Manji J, Wilcox PG, Javer AR, Buxton JA, Quon BS. A systematic review of factors associated with health-related quality of life in adolescents and adults with cystic fibrosis. Ann Am Thorac Soc 2015; 12(3):420–8. [7] Solem CT, Vera-Llonch M, Liu S, Botteman M, Castiglione B. Impact of pulmonary exacerbations and lung function on generic health-related quality of life in patients with cystic fibrosis. Health Qual Life Outcomes. Health Qual Life Outcomes 2016;14(1):63. [8] Kelemen L, Lee AL, Button BM, Presnell S, Wilson JW, Holland AE. Pain impacts on quality of life and interferes with treatment in adults with cystic fibrosis. Physiother Res Int 2012;17(3):132–41. [9] Lee AL, Rawlings S, Bennett KA, Armstrong D. Pain and its clinical associations in individuals with cystic fibrosis: a systematic review. Chron Respir Dis 2016;13(2):102–17.

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Please cite this article as: Maras D, et al, Breathlessness catastrophizing relates to poorer quality of life in adults with cystic fibrosis, J Cyst Fibros (2018), https://doi.org/ 10.1016/j.jcf.2018.08.008