Abstract
Symptom burden is a key component of health-related quality of life (HRQOL) in patients with cystic fibrosis (CF). In order to examine symptom prevalence and characteristics of adults with CF, we administered the Memorial Symptom Assessment Scale (MSAS), a previously validated measure of symptom burden, to CF patients enrolled in the Project on Adult Care in CF (PAC-CF). The mean age of the 303 respondents (response rate 91%) was 32.8 years (range 19–64); 58% were female, and their mean baseline pulmonary function (FEV1 % predicted) was 69% (SD 28%). The median number of symptoms reported was 10, and there was no difference in the number of symptoms reported based on age, gender, or FEV1. The most prevalent symptoms were cough (94%), shortness of breath (77%), and lack of energy (77%). Lack of energy and irritability caused the highest level of distress. MSAS symptom subscales were only moderately correlated with symptom status domains from existing CF HRQOL measures. Factor analysis led to the development of three distinct MSAS CF-symptom subscales, each with high internal validity. These findings show that adults with CF have a high symptom burden, particularly with respiratory and psychological symptoms, and that the new MSAS CF specific subscales are a reliable measure of symptom distress in the CF population.
Keywords: Cystic fibrosis, symptom burden, symptom prevalence
Introduction
Over the past several decades, the survival of patients with cystic fibrosis (CF) has increased, leading to a growing population of adults living with CF as a chronic illness. In 2004, over 40% of the US CF patient population was over the age of 18, and the median predicted survival for patients with CF has now reached 36 years.1 The emergence of a larger population of adults living with CF necessitates further understanding of their overall health related quality of life (HRQOL). Such HRQOL outcomes are becoming increasingly important in clinical care as well as in therapeutic trials for adults with CF.2
Symptom status is one component of HRQOL in patients with any chronic disease.3 Adults with CF would be expected to experience a broad range of symptoms as a result of the respiratory and gastrointestinal manifestations of their disease. In particular, changes in respiratory and constitutional symptoms are used in the definitions of a CF pulmonary exacerbation leading to intensification of CF-specific treatments and hospitalizations.4 Nutritional status, which has been linked to outcomes in CF, can be influenced by symptoms such as chronic abdominal pain, nausea, and poor appetite. Finally, living with CF has been associated with significant psychological symptoms.5 Most prior studies in adults with CF have focused on individual groups of symptoms such as cough6, sleep disturbances7, pain8, and depression.9 In addition, these studies have focused on the occurrence of symptoms rather than symptom burden, which has been defined as a composite measure including symptom prevalence, severity, and distress felt by an individual as a result of symptoms.10 No prior study has comprehensively evaluated symptom burden in a large population of adults with CF.
As part of an ongoing longitudinal study of quality of life in adults with CF, we obtained information about the prevalence and impact of a range of physical and psychological symptoms using the Memorial Symptom Assessment Scale (MSAS), a previously validated measure of symptom burden. 10 Our aim was to describe the overall symptom burden of CF as reported by adults living with the disease and to assess the reliability and validity of the original MSAS subscales in this population.
Methods
Study Participants
The Project on Adult Care in Cystic Fibrosis (PAC-CF) is an ongoing prospective, longitudinal panel study of adults with CF. Adults 18 years of age or older receiving care at one of ten participating CF Centers were eligible for the study. The study coordinator at each participating CF Center provided, without any identifying information, age, gender, and the following clinical variables from 2003: maximum FEV1%, weight-for-age Z-score, frequency of pulmonary exacerbations, presence of diabetes, colonization with Burkholderia Cepacia complex and Staphylococcus aureus, and pancreatic sufficiency. These data were used to calculate each individual’s predicted probability of surviving 5 years, using Liou et al.’s rigorously developed prognostic model.11 All adults with a predicted probability of 5-year survival less than 0.975 (n=515) and a randomly selected 25% of adults with a predicted probability of 0.975 or higher (n=60) were recruited for the study beginning in Fall 2004. This stratified sampling design was adopted because adults with a very high predicted probability of survival were least informative with respect to the overall PAC-CF goal of examining trends over time in quality of life as CF progresses. The study protocol was approved by the Institutional Review Boards at Educational Development Center, Inc., Children’s Hospital Boston, and the other nine hospitals in which the participating CF Centers are located.
A total of 333 (301 with predicted survival less than or equal to 0.975 and 32 with predicted survival greater than 0.975) adults with CF enrolled in the study. The data presented here are from the first survey of PAC-CF, administered to 326 participants in April 2005. Between enrollment and administration of the first survey, three participants died and four received a lung transplant and thus were no longer eligible for the study.
Measures
Symptom burden was assessed with the Memorial Symptom Assessment Scale (MSAS), a symptom scale that has been previously validated in patients with cancer, heart disease, HIV, and chronic critical illness.12–15 The MSAS evaluates the symptom severity, frequency, and distress using separate 4- or 5-point Likert scales for each dimension. We evaluated 22 symptoms using two MSAS symptom groups, high prevalence physical (PHYS-H) symptoms and psychological (PSYCH) symptoms, and added one additional symptom, sinus discharge and/or pain, due to its relatively high prevalence among patients with CF.16 Each individual symptom score was calculated as the average score on the severity, frequency, and distress scales. If a respondent did not report having the symptom, the symptom score was zero. Three previously validated subscales were also calculated.10 The MSAS-PSYCH subscale is the average of symptom scores for six psychological symptoms, the MSAS-PHYS subscale is the average of the symptom scores for 11 physical symptoms, and the Global Distress Index (MSAS-GDI) is the average of frequency scores for four prevalent psychological symptoms and distress scores for six prevalent physical symptoms. The scores for each of the symptoms and subscales range from 0–4, with a higher score representing a higher symptom burden.
The PAC-CF survey also included questions from the adolescent and adult version of the Cystic Fibrosis Questionnaire (CFQ-R)17 and the Cystic Fibrosis Quality of Life (CFQoL),18 two CF-specific measures of HRQOL. The symptom status subscales from these HRQOL measures were used to assess the concurrent validity of the MSAS subscales in this population. The CFQ-R, which was validated in a national sample of adults with CF, provided three measures of symptom status, respiratory symptoms, digestive symptoms, and weight. In addition, the measure of emotional state, which asked about the degree to which the respondent felt worried, sad, lonely, and had difficulty making plans for the future, was used as a measure of psychological status. The Chest subscale from the CFQoL, which was developed and validated in the United Kingdom, provided an additional measure of respiratory symptoms. The score for each of these scales was standardized on a 0- to 100-point scale on which higher scores represent lower symptom frequency.
Statistical Analysis
Descriptive statistics, calculated using sample selection weights (the inverse of the probability of selection) to adjust for the disproportionate stratified sampling design, were used to summarize the demographic and clinical characteristics of the PAC-CF sample and to describe the prevalence and characteristics of individual symptoms and overall symptom burden. Differences in prevalence and MSAS subscales by respondent age, gender, and FEV1 were assessed using weighted chi-square test of independence, t-test, or ANOVA, as appropriate. Respondents were divided into four age groups: 18–24, 25–34, 35–44, and 45+ and three groups based on their best FEV1 (% predicted) in 2004: less than 40%, 40–69%, and 70% and greater.
Cronbach’s alpha was calculated to assess the internal consistency reliability of the MSAS subscales in the adult CF population. Pearson product-moment correlation coefficients between the symptom status subscales from the CFQ-R and CFQoL and the MSAS subscales were computed to assess concurrent validity. To assess construct validity, we conducted a principal-axis factor analysis with direct oblimin rotation. A scree test was used to identify the number of factors. All analyses were performed with SAS software version 9.1 (SAS Institute, Cary, NC) and a P-value < 0.05 was considered statistically significant.
Results
Prevalence of Symptoms
Table 1 presents the clinical and demographic characteristics of the 303 CF adults who responded to the first PAC-CF survey (response rate 93%). Of the 22 symptoms assessed, respondents reported experiencing a median of 10 total symptoms (IQR 6–13), with a median of six physical symptoms (IQR 4–8) and three psychological symptoms (IQR 1–5). Symptom prevalence ranged from 14–94% for each individual symptom (Table 2). Cough was the most prevalent symptom (94%), followed by shortness of breath (77%), lack of energy (77%), and sinus pain and discharge (66%). Psychological symptoms were reported by the majority of respondents, with worrying (67%), feeling irritable (60%), difficulty sleeping (57%), and feeling sad (56%) reported by the highest number. Gastrointestinal symptoms such as vomiting, change in taste, weight loss, and nausea had much lower prevalence than both respiratory and psychological symptoms. Females were more likely to report cough (P=0.03), nausea (P=0.01), feeling bloated (P=0.02), lack of energy (P=0.03), feeling irritable (P=0.006), and worrying (P=0.04). FEV1 was negatively associated with reporting cough (P =0.04), shortness of breath (P ≤ 0.0001), and lack of energy (P =0.007), and was positively associated with reporting constipation (P =0.01) and feeling bloated (P =0.01). The reporting of any individual psychological symptom was not associated with FEV1. Age was not associated with prevalence of any of the symptoms assessed. There was no significant association between age (P =0.4), gender (P =0.1), or FEV1 (P =0.3) and the total number of symptoms reported by an individual.
Table 1.
Clinical Characteristics of the PAC-CF Cohort
| Summary Statisticsa | |
|---|---|
| Number of Respondents (n) | 303 |
| % Female | 58% |
| Age (years) (Mean ± SD) | 32.8 ± 13.2 |
| FEV1 (% predicted) (Mean ± SD) | 69 ± 28 |
| Weight Z Score (Mean ± SD) | −0.12 ± 1.3 |
| Pulmonary Exacerbations in 2004 (Median, IQR) | 1 (0,2) |
| Pancreatic Insufficient | 85% |
Descriptive statistics were calculated using sample selection weights to adjust for the disproportionate stratified sampling design.
Table 2.
Symptom Prevalence and Burden Among Adults with CF Enrolled in PAC-CF
| % of those reporting each individual symptom | |||||
|---|---|---|---|---|---|
| Symptom | % Reporting Symptom | Mean Symptom Score (SD) | % Reporting High Frequencya | % Reporting High Severity b | % Reporting High Distressc |
| Cough | 94% | 1.9 (1.0) | 64 | 72 | 20 |
| Shortness of breath | 77% | 1.4 (1.3) | 32 | 56 | 26 |
| Lack of energy | 77% | 1.6 (1.5) | 43 | 66 | 31 |
| Worrying | 67% | 1.3 (1.4) | 31 | 64 | 27 |
| Sinus discharge | 66% | 1.2 (1.5) | 39 | 56 | 20 |
| Feeling irritable | 60% | 1.1 (1.4) | 32 | 60 | 30 |
| Feeling drowsy | 57% | 1.0 (1.3) | 32 | 51 | 18 |
| Difficulty sleeping | 57% | 1.2 (1.5) | 43 | 69 | 28 |
| Feeling sad | 56% | 1.0 (1.4) | 26 | 52 | 22 |
| Feeling bloated | 51% | 0.9 (1.4) | 32 | 59 | 20 |
| Diarrhea | 44% | 0.7 (1.1) | 18 | 39 | 13 |
| Pain | 43% | 0.8 (1.4) | 33 | 61 | 24 |
| Feeling nervous | 42% | 0.8 (1.3) | 31 | 59 | 17 |
| Difficulty concentrating | 40% | 0.7 (1.2) | 22 | 51 | 22 |
| Dry mouth | 35% | 0.5 (1.0) | 19 | 42 | 6 |
| Lack of appetite | 33% | 0.5 (1.1) | 23 | 53 | 17 |
| Nausea | 30% | 0.5 (1.1) | 23 | 39 | 19 |
| Constipation | 28% | 0.5 (1.2) | 25 | 62 | 27 |
| Dizziness | 27% | 0.5 (1.1) | 21 | 41 | 25 |
| Weight loss | 23% | 0.4 (1.0) | 30 | 42 | 25 |
| Vomiting | 15% | 0.2 (0.8) | 6 | 45 | 26 |
| Change in taste | 14% | 0.2 (0.7) | 14 | 35 | 12 |
Descriptive statistics were calculated using sample selection weights to adjust for the disproportionate stratified sampling design
Reporting frequency as frequently or almost constantly
Reporting severity as moderate, severe, or very severe
Reporting distress as somewhat, quite a bit, or very much
AU: THERE WAS NO CORRESPONDING * IN THE TABLE TO MATCH THE LEGEND. DELETE * OR ADD TO TABLE WITH APPROPRIATE SUPERSCRIPTED LETTER
MSAS symptom scores, calculated by averaging responses to frequency, severity, and distress ratings, ranged from 0.2 – 1.9 (Table 2). Cough was reported as high frequency by 64% of respondents who reported having had cough. With all of the other symptoms, less than half of the respondents reported high frequency when reporting a particular symptom. Among the subset of patients reporting the presence of a symptom, moderate to high severity was reported by >50% of respondents for 13 symptoms, including all the three major CF respiratory symptoms (cough, shortness of breath, and sinus pain) and all six psychological symptoms. Sixty-one percent of those who reported pain also reported it to be of moderate to high severity. For each individual symptom, only a minority of respondents indicated that any particular symptom caused high distress. High distress was seen most commonly among those who reported worrying (31%) and feeling irritable (30%).
Reliability and Validity of the Original MSAS Subscales in the Population of Adults with CF
The mean subscale scores for the three validated MSAS subscales are presented in Table 3. Cronbach’s alpha coefficients for all of the subscales were high: MSAS-PHYS (0.92), MSAS-PSYCH (0.95), MSAS-GDI (0.82). The subscale scores were only moderately correlated with symptom status measures from CFQ-R and CFQoL (Table 3). The MSAS-PHYS subscale was moderately correlated with measures of respiratory and digestive symptom status as well as emotional state. In contrast, the MSAS-PSYCH subscale was strongly with emotional state (P = −0.69), but only moderately correlated with measures of respiratory and digestive symptom status. Similarly, the MSAS-GDI subscale was strongly correlated with emotional state (P= −0.69) and chest symptoms (P = −0.53), but only moderately or weakly correlated with the CFQ-R measure of respiratory symptoms, digestive symptoms, and weight.
Table 3.
MSAS Subscale Scores in CF Adults
| MSAS Subscales | |||
|---|---|---|---|
| MSAS-PHYS | MSAS-PSYCH | MSAS-GDI | |
| Mean Score (SD) a | 0.6 (0.6) | 1.0 (1.0) | 0.9 (0.9) |
| Cronbach’s alpha | 0.92 | 0.95 | 0.82 |
| Correlation with measures of Symptom Status | |||
| Respiratory Symptomsb | −0.40d | −0.34v | −0.39 d |
| Chest Symptomsc | −0.51 d | −0.49 d | −0.53 d |
| Weightb | −0.21 d | −0.11 | −0.18 d |
| Digestive Symptomsb | −0.45 d | −0.33 d | −0.40 d |
| Emotional Stateb | −0.51 d | −0.69 d | −0.69 d |
Descriptive statistics were calculated using sample selection weights to adjust for the disproportionate stratified sampling design.
CFQ-R Domains.
CFQoL Domains.
P <0.05.
Since the MSAS symptom subscales were developed in a cancer patient population, the overall subscale scores were lower than those previously reported in other patient populations,12–15 and the pattern of correlations between the original MSAS subscales and CF-specific measures of symptom status called into question the convergent and discriminant validity of the original MSAS subscales. We, therefore, conducted a factor analysis to assess whether a different factor structure existed for adults with CF. This analysis found that symptoms clustered around three distinct factors (Table 4). The first cluster (MSAS-CFPSYCH) included five of the six psychological symptoms comprising the MSAS-PSYCH subscale. The sixth symptom, difficulty sleeping, clustered with five other respiratory and constitutional symptoms (MSAS-CFRESP): cough, shortness of breath, lack of energy, sinus pain and/or discharge, and pain. A third cluster included four GI symptoms (MSAS-CFGI); lack of appetite, weight loss, vomiting, and nausea. Seven symptoms had low factor loadings and were not included in any of the CF subscales.
Table 4.
Factor Analysis of MSAS Symptom Scale in the PAC-CF Cohort
| Symptom | Factor 1 | Factor 2 | Factor 3 |
|---|---|---|---|
| MSAS-CFPSYCH | |||
| Worrying | 0.74287 | 0.01044 | −0.06497 |
| Feeling sad | 0.70945 | 0.02432 | −0.01342 |
| Feeling nervous | 0.68039 | −0.03837 | −0.01730 |
| Feeling irritable | 0.57581 | 0.07790 | 0.08227 |
| Difficulty concentrating | 0.55622 | 0.00038 | 0.03037 |
| MSAS-CFRESP | |||
| Cough | 0.06538 | 0.63809 | 0.15404 |
| SOB | 0.07976 | 0.63577 | 0.16373 |
| Lack of energy | 0.23467 | 0.55384 | 0.10017 |
| Sinus discharge | −0.08463 | 0.54868 | −0.15919 |
| Pain | 0.08581 | 0.41008 | 0.08649 |
| Difficulty sleeping | 0.20150 | 0.37006 | 0.05438 |
| MSAS-CFGI | |||
| Lack of appetite | 0.00980 | 0.14486 | 0.69415 |
| Weight loss | 0.19160 | −0.08066 | 0.64980 |
| Vomiting | −0.05109 | −0.00335 | 0.64047 |
| Nausea | 0.02737 | 0.02442 | 0.61738 |
AU: PLEASE DEFINE BOLDED NUMBERS
The highest subscale score was for the MSAS-CFRESP scale (1.4 ± 0.9), followed by the MSAS-CFPSYCH (1.0 ± 1.1). The MSAS-CFGI subscale had the lowest mean score (0.4 ± 0.8) (Table 5). Cronbach’s alpha coefficients for all three of these subscales were high. Scores on the CF respiratory subscale (MSAS-CFRESP) were strongly correlated with measures of respiratory status from CFQ-R and CFQoL, moderately correlated with the CFQ-R measures of emotional state, but only weakly correlated with measures of gastrointestinal-related symptoms. The MSAS-CFGI subscale was the only subscale with a moderate correlation with the CFQ-R weight domain (P = −0.49). The MSAS-CFPSYCH scores had a high correlation with emotional state (P = −0.69), but were less strongly correlated with respiratory and GI symptom domains. These patterns of correlations support the convergent and discriminant validity of these new CF-specific measures of symptom burden.
Table 5.
MSAS CF-Specific Subscales
| MSAS CF SUBSCALES | |||
|---|---|---|---|
| MSAS-CFRESP | MSAS-CFGI | MSAS-CFPSYCH | |
| Mean Score (SD) a | 1.4 (0.9) | 0.4 (0.8) | 1.0 (1.1) |
| Cronbach’s alpha | 0.81 | 0.74 | 0.86 |
| Correlation with measures of symptom status | |||
| Respiratory Symptomsb | −0.60d | −0.31 d | −0.28 d |
| Chest Symptomsc | −0.70 d | −0.42 d | −0.43 d |
| Weightb | −0.10 | −0.49 d | −0.11 |
| Digestive Symptomsb | −0.32 d | −0.19 d | −0.32 d |
| Emotional Stateb | −0.56 d | −0.35 d | −0.69 d |
Descriptive statistics were calculated using sample selection weights to adjust for the disproportionate stratified sampling design.
CFQ-R Domains.
CFQoL Domains.
P <0.05.
Overall Symptom Burden in CF Adults Based on Clinical Characteristics
Table 6 presents the MSAS CF subscale scores reported by PAC-CF respondents based on gender, age, and baseline pulmonary function. Respiratory and psychologic symptom burden was higher in females and in respondents with lower baseline pulmonary function (FEV1 <40% predicted). Respondents with lower pulmonary function also reported a higher GI symptom burden. Symptom burden subscale scores did not significantly differ based on respondent age.
Table 6.
MSAS CF Subscale Scores Based on Gender, Age, and Pulmonary Function
| MSAS CF SUBSCALES | |||
|---|---|---|---|
| MSAS-CFRESP | MSAS-CFGI | MSAS-CFPSYCH | |
| Mean Scorea | 1.4 (0.9) | 0.4 (0.8) | 1.0 (1.1) |
| Gender | |||
| Female | 1.5 (0.9) b | 0.4 (0.8) | 1.1 (1.1) b |
| Male | 1.3 (0.9) | 0.3 (0.6) | 0.8 (1.0) |
| Age (Years) | |||
| 18–24 | 1.4 (1.0) | 0.4 (0.8) | 0.9 (1.3) |
| 25–34 | 1.5 (0.9) | 0.6 (0.9) | 1.0 (1.0) |
| 35–44 | 1.4 (1.1) | 0.3 (0.6) | 1.1 (1.1) |
| >45 | 1.4 (0.8) | 0.2 (0.5) | 0.8 (0.9) |
| FEV1 (% predicted) | |||
| <40% | 1.6 (0.7) b | 0.5 (0.6) b | 1.0 (0.8) b |
| 40–69% | 1.4 (0.8) | 0.5 (0.7) | 1.1 (1.0) |
| >70% | 1.3 (1.2) | 0.3 (0.8) | 0.8 (1.2) |
Descriptive statistics were calculated using sample selection weights to adjust for the disproportionate stratified sampling design.
P < 0. 05.
Discussion
In this prospective cohort study of adults with CF, we used the MSAS to describe the prevalence, frequency, severity, and distress from both physical and psychological symptoms in this population of adults with a lifelong chronic illness. Our results confirm the presence of a varied number of symptoms among this unique patient population, with a high prevalence of both respiratory and psychological symptoms. As expected, the most prevalent symptoms reported were respiratory, particularly cough and shortness of breath. Other symptoms related to the chronic respiratory compromise of CF, such as fatigue and sleep disturbances, were also common. The majority of respondents reported difficulty sleeping, and many also reported a high frequency of such disturbances. This finding is similar to prior work on sleep disturbances in CF adults demonstrating chronic sleep loss and nocturnal hypoxia during overnight polysomnography.19
Interestingly, our results demonstrate a high prevalence of psychological symptoms among adults with CF. Over one-half of our sample reported worrying, feeling irritable, and feeling sad. Among respondents reporting each individual symptom, the psychological symptoms provoked the highest percentage reporting high distress. These results are consistent with prior studies showing significant psychological symptoms in CF patients, particularly depression,5 and underscores the importance of psychological screening and support for all adults with CF. Pain symptoms were reported by over 40% of our cohort, with more than one-third of those experiencing pain reporting it as high frequency. We did not assess the nature of these pain symptoms in this survey. Prior work in children with CF has demonstrated a high level of both acute and chronic pain.8 Given the relatively high prevalence of pain reported by our CF adult population, further study of pain assessment, treatment, and intervention in this patient population is necessary.
Psychological and respiratory symptoms were much more prevalent than gastrointestinal symptoms, despite the fact that most of the respondents have pancreatic insufficiency and might be expected to report resultant abdominal symptoms. Since pancreatic insufficiency and malabsorption in CF are treatable with enzyme supplementation, the lower prevalence of GI symptoms may simply reflect the relative ease of managing this aspect of CF as opposed to the more difficult to treat pulmonary and psychological manifestations of chronic respiratory disease.
Although symptom prevalence for many symptoms was relatively high, individual symptom scores, incorporating measures of symptom frequency, severity, and distress, were relatively low. In fact, most individuals did not report high distress for the most prevalent respiratory symptoms, suggesting the possibility of some level of adaptation to symptoms such as cough, sinus pain, and shortness of breath over time. In contrast, fatigue and irritability were reported to cause high distress in almost one-third of patients with these symptoms. Interventions aimed at reducing the distress caused by such global chronic disease manifestations therefore warrant further study in CF adults, perhaps proceeded by qualitative research to better understand the impact and meaning of various symptoms on the illness experience in CF.
The symptom scores among our cohort of CF adults are similar in magnitude to scores described in an outpatient population of adult cancer patients.12 Interestingly, the scores are lower than those reported for cancer inpatients, HIV outpatients, and those with chronic critical illness.13–15 Since CF leads to a different constellation of symptoms than these other chronic illnesses, we used factor analysis to identify whether different symptom clusters exist in CF. Though more formal validation is warranted, this analysis resulted in two distinct subscales encompassing respiratory (MSAS-CFRESP) and GI (MSAS-CFGI) symptoms, and a psychological subscale which was similar to the existing MSAS-PSYCH subscale. Each of the subscales had a high internal validity, and could be used in future work assessing symptoms in adult CF populations. The MSAS-CFRESP subscale, including high prevalence respiratory symptoms as well as sleep disturbance, pain, and lack of energy, generated the highest subscale score in our population. The finding that sleep disturbance and fatigue clustered with respiratory symptoms in the MSAS-CFRESP subscale suggests that these symptoms are more closely associated with chronic respiratory symptoms, and possibly nocturnal hypoxia, rather than with psychological manifestations of chronic disease. Overall, the higher respiratory and psychological subscale scores suggest that these particular symptoms need to be assessed and treated in routine clinical care of adults with CF.
Symptom prevalence and symptom burden as measured by the composite MSAS CF subscales did differ in a few important areas by gender and baseline pulmonary function. We did find a few gender differences in symptom prevalence, particularly in psychological and GI symptoms. Females also reported a higher overall respiratory and psychological symptom burden. Such gender differences have been described in other studies of CF QOL and warrant further study.20 Respondents with higher baseline pulmonary function did report less cough and shortness of breath, but the prevalence of psychological symptoms did not vary by a respondent’s pulmonary function. As expected, overall symptom burden was also higher in CF adults with severely impaired lung function, as this subgroup of respondents had higher subscale scores in all 3 of the MSAS CF symptom burden measures. Interestingly, age was not associated with symptom prevalence or overall symptom burden, suggesting that CF disease severity impacts symptom burden in CF more than the number of years that an individual has survived with chronic disease.
Our analysis is a cross-sectional approach to symptom burden in an adult CF population, and does not allow us to determine whether symptom burden changes over time, particularly as disease progresses. Future evaluation of the MSAS CF-specific symptom subscales will be necessary in order to establish reliability and validity and assess for responsiveness to change over time, and we are continuing such evaluation within the PAC-CF cohort. We also did not assess whether symptom burden was influenced by differences in treatments used by patients, though we can speculate that undertreatment of respiratory exacerbations, CF-related gastrointestinal disease, or psychological manifestations secondary to chronic illness would result in reporting a higher symptom burden. Future work will also address whether symptom burden is associated with other measures of CF-related QOL, particularly functional status.
In the conceptual model of HRQOL proposed by Wilson and Cleary,3 symptom status occupies a critical point along the pathway describing overall HRQOL. Prior work on CF-specific HRQOL measures has incorporated several aspects of symptom status.20, 21 Acute symptoms, as reflected by CF pulmonary exacerbations, have been shown to negatively impact HRQOL in CF.22 In this study, we found that symptom burden, measured at a time of relative clinical stability in CF, is also correlated with the symptom status domains of existing CF HRQOL measures. In particular, the MSAS-CFRESP and MSAS-GDI subscales are negatively correlated with the HRQOL domains of respiratory and chest symptoms, the PSYCH subscales are most negatively correlated with the emotional state domain, and the MSAS-CFGI subscale is most negatively correlated with weight. Therefore, by providing a comprehensive assessment of symptom burden, including severity, frequency, and distress, the MSAS subscales add important information on the overall symptom status of CF adults.
In summary, our results indicate that assessment of symptom burden in CF adults requires attention to both the physical and psychological manifestations of chronic respiratory disease. Initial analysis of symptom clustering in adults with CF suggests that the new CF-specific subscales derived from the MSAS may provide additional patient-reported outcomes that may have a role in both clinical care and research in CF adult populations.
Acknowledgments
This work was supported by a grant from the National Heart, Lung, Blood Institute (R01 HL72938).
Footnotes
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