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Health-Related Quality of Life Among Patients With Idiopathic Pulmonary Fibrosis* FREE TO VIEW

Jeffrey J. Swigris, DO, MS; Michael K. Gould, MD, MS, FCCP; Sandra R. Wilson, PhD
Author and Funding Information

*From the Division of Pulmonary and Critical Care Medicine (Dr. Swigris), Stanford University Medical Center, Stanford; VA Palo Alto Health Care System (Dr. Gould), Palo Alto; and Palo Alto Medical Foundation (Dr. Wilson), Palo Alto, CA.

Correspondence to: Jeffrey J. Swigris, DO, Stanford University Medical Center, Division of Pulmonary and Critical Care Medicine, MC5236, Room H3143, 300 Pasteur Dr, Stanford, CA 94305-5236; e-mail: jswigris@stanford.edu



Chest. 2005;127(1):284-294. doi:10.1378/chest.127.1.284
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Published online

The hallmark of idiopathic pulmonary fibrosis (IPF) is relentless and progressive breathlessness culminating in respiratory failure and death. Clinicians and investigators are increasingly aware that many patients with chronic diseases, like IPF, value the quality of their lives as much or more than their length of survival. Despite this growing awareness, little research has focused on quality of life (QOL) in IPF patients. Nevertheless, the few studies that have been performed uniformly show the negative impacts of IPF on QOL, particularly in the areas of physical health, energy, and symptoms. To fill important knowledge gaps, more research is needed. For example, future studies in well-defined IPF patient populations should rigorously assess the psychometric properties of different measures of QOL. Currently, there is no disease-specific instrument for use in patients with IPF. A carefully developed, IPF-specific instrument that includes items most relevant to IPF patients should be more sensitive to change than existing generic or non-IPF respiratory disease-specific instruments. Longitudinal assessments are needed to map the trajectory of QOL in relation to disease progression and to reveal whether different aspects of QOL become impaired over time. Addressing these research opportunities will markedly improve our knowledge of this outcome, which is highly valued by patients. These endeavors will also help clinicians who care for patients with IPF to develop a better understanding of its profound negative impact, and it will help future IPF clinical investigators to select the most valid, reliable, and appropriate QOL instrument to fill the roles their studies require.

Idiopathic pulmonary fibrosis (IPF) is a deadly disease with a prevalence ranging from 7 to 20 cases per 100,000 people in the general population to perhaps as many as 175 cases per 100,000 people who are ≥ 75 years of age.1The diagnosis is established when a surgical lung biopsy specimen shows a usual interstitial pneumonia pattern of lung injury (when other causes of lung fibrosis are absent) or by clinical criteria, which were outlined in an international consensus statement.2 Progressive breathlessness dominates the clinical picture, and commonly results in respiratory failure and death.23 Conventional IPF pharmacotherapy is associated with frequent adverse reactions, and we lack convincing evidence that these medications improve morbidity, physiologic or radiologic markers of disease severity, or survival.4

While halting disease progression and improving survival have long been the focus of IPF treatment, improving quality of life (QOL) is extremely important for many patients and is perhaps a more realistic goal at this time. Despite the apparent substantial toll that the disease has on physical, emotional, social, and other aspects of patients’ lives, research focused on QOL in IPF has been limited. However, in the last 5 years, several studies have examined QOL in patients with IPF. Given this growing emphasis and the great value that patients place on this outcome measure, it is imperative that IPF investigators and clinicians develop a clearer understanding of how this disease impacts patients’ QOL.

In this review, we aim to summarize the existing knowledge of health-related QOL (HRQL) in IPF patients. We first define some of the key terminology used in HRQL research (additional terms and their definitions can be found in the “Appendix”). Because many of the published studies on HQRL in IPF patients are instrument “validation” studies, we discuss validity in slightly more detail than some of the other concepts. Then, we examine what is known about HRQL in IPF patients. Next, we highlight gaps in our knowledge of issues related to HRQL in this disease. We conclude by outlining research opportunities that will advance our understanding of IPF, its impact on the quality of patients’ lives, and our ability to measure that impact.

QOL and HRQL

QOL refers to a person’s “holistic” evaluation of satisfaction with his own life in areas (domains) that he considers to be important.58 Accordingly, one aspect of an individual’s QOL may seem to others to be significantly impaired, but if that aspect is unimportant to the individual, his perceived impairment could be minimal or nil.

According to the World Health Organization (WHO), health not only affects other life domains, it encompasses many of them. Health includes aspects of well-being (or lack thereof) in the physical, mental, emotional, social, and spiritual facets of life.9 In the broadest terms, HRQL incorporates the subjectively perceived impact of one’s health (as defined here) on life domains of perceived importance,5,8,10 and the instruments that measure HRQL attempt to quantify those perceptions. In this article, we use the term HRQL (except when referring specifically to the WHO QOL assessment 100-item instrument [WHOQOL-100], a generic QOL instrument) because we are most interested in examining how IPF and its treatment impact QOL.

HRQL Instruments

Unlike generic QOL instruments, which tap a wide array of domains (with aspects of health usually incorporated into one or more of them), HRQL instruments focus only on domains impacted by health. They come in the following two varieties: (1) generic instruments; and (2) disease-specific instruments. Because they are tailored to patients with a certain disease or condition, disease-specific instruments are likely to be more sensitive to changes in a patient’s status than generic QOL instruments or even generic HRQL instruments.

Reliability and Validity

To serve meaningful roles, HRQL instruments must produce reliable and valid results. An instrument is reliable if it measures something in a reproducible way. Validity refers to whether an instrument truly measures what it intends to measure and whether its scores convey important information about particular attributes of the people who produce them.11

To “validate” an HRQL instrument for IPF, we must establish the meaning of its scores and also support the inference that its scores can be used confidently for an intended purpose in this population. For example, can scores predict disease progression or survival? What is the relationship between changes in scores and changes in disease status within an individual? What do instrument scores tell us about patients’ concurrent clinical characteristics?

The first question deals with predictive validity, while the last two deal with concurrent validity. Establishing concurrent validity involves demonstrating that a hypothesized pattern of associations (correlations) exists between certain concurrently collected clinical parameters (hypothesized to also provide information about HRQL) and the instrument scores.1213 For example, we might hypothesize that IPF patients with low FVC values, dyspnea, and low oxygen saturation levels at rest would have impaired HRQL in domains concerning physical health.

Since there is no reference “gold standard” for the psychological construct HRQL, we must use the clinical parameters as points of reference. We do not expect perfect or even very high correlations, as these would suggest that the instrument is unable to provide unique information. However, we do expect the correlations to be in directions and of magnitudes that make sense in terms of our concept of HRQL.

Validity is population-specific and use-specific. An HRQL instrument might be valid for performing a role in one population but not valid for the same role in a different population. Moreover, it being valid for one purpose in a population does not guarantee that it is valid for another purpose in that population. For example, an instrument’s concurrent validity does not necessarily ensure its suitability for assessing HRQL longitudinally. Thus, ideally, we should establish an instrument’s validity for a particular purpose in the very population and under similar circumstances to those in which we will use the instrument in future studies. To date, studies of HRQL in patients with IPF have not examined the ability or an instrument to assess HRQL longitudinally.

Domains Impacted

Only a handful of studies have measured HRQL (or QOL) in patients with IPF (Table 1 ). Collectively, the investigators that performed these studies used five different instruments to measure HRQL, including two disease-specific HRQL instruments developed for patients with obstructive lung disease, two generic HRQL instruments, and one generic QOL instrument (Table 2 ). While the studies vary in their case definitions of IPF, inclusion criteria, and reporting of instrument scores, the common message among them is that, relative to the general population, IPF patients have significantly impaired HRQL and QOL.

De Vries and colleagues14conducted three focus groups with a total of 10 Dutch IPF patients to examine the life domains that were impacted the most by IPF. The mean age of the patients was 61 years, the diffusing capacity of the lung for carbon monoxide (Dlco) was 48% of predicted normal, and their Pao2 at rest was 69 mm Hg. Patients completed and discussed the St. George Respiratory Questionnaire (SGRQ) and the WHOQOL-100. The SGRQ is an instrument that was developed specifically for patients with chronic airflow obstruction, and it contains domains that assess respiratory symptoms (ie, the symptoms domain), the overall impact of respiratory disease on the respondent’s life (ie, the impacts domain), and physical activities that either cause or are limited by dyspnea (ie, the activities domain).15 Higher SGRQ scores (on each of the three subscales or the total instrument score) connote greater distress and, thus, worse HRQL.

In the focus groups, participants described their lives as being “centered” on their disease. They noted a constant awareness of having IPF and emphasized the physical limitations that it imposes, as follows: “all their activities need to be paced.” Reflecting this, the mean scores of participants on the SGRQ activity subscale were much higher (worse) than for the symptoms and impacts subscales. Participants also said that IPF caused fatigue and social isolation, which were both viewed as “serious problems.” Other general areas that were perceived to be negatively affected by IPF included mobility, leisure activities, social relations, working capacity, and energy levels.

In another study, De Vries et al16examined QOL (as opposed to HRQL) in 41 patients with biopsy-proven IPF and 41 age-matched healthy control subjects using the WHOQOL-100. This is a cross-cultural, generic, multidimensional QOL instrument that was designed simultaneously in 15 WHO field centers around the world.17 It includes 4 general items, addressing perceived QOL and general health, and another 96 items that are divided equally into 24 facets. The facets are grouped into the following six domains: physical health; psychological health; level of independence; social relations; environment; and spirituality/religion/beliefs. Scores for each facet and domain range from 4 to 20, with higher scores indicating better QOL.

Compared to control subjects, the 41 IPF patients had significantly worse QOL in the overall QOL and in the general health, physical health (which assesses energy, pain, and sleep), and level of independence domains. However, the scores of IPF patients for the psychological health, social relationships, and spirituality subscales revealed that their QOL in these domains was not different from that of control subjects.

Martinez et al18compared HRQL in 34 Brazilian IPF patients to 34 healthy control subjects using the Medical Outcomes Study 36-item short form (SF-36) instrument. The SF-36 is a generic HRQL instrument with 36 questions divided into eight subscales.1920 It has been extensively used and validated in patients with other respiratory and nonrespiratory conditions.2122 In addition to reporting scores for the individual subscales, investigators can report scores for two psychometrically derived summary measures, the physical component summary and the mental component summary.

In this study, IPF subjects had significantly worse HRQL than control subjects in all domains assessed by the SF-36 except bodily pain, however, HRQL was most impaired in domains concerning physical health. For example, the IPF patient’s role-physical subscale score, which examines the extent to which physical health interferes with work or other daily activities,23 and their physical functioning subscale score, which examines the limitations in physical activity imposed by health, were lowest and most disparate from the control group. The IPF patients also endured a greater negative impact of emotional problems on work or daily activities than control subjects.

In another study, Martinez and colleagues24 again used the SF-36 to evaluate HRQL in 30 patients with moderate IPF. The mean scores were lower than normal (US adult population) values on all subscales except bodily pain. As observed in the previous study, HRQL was most impaired in domains that focused on physical health and physical activity. After the role-physical and physical functioning subscales, the greatest deviation in scores from normal values occurred on the social functioning subscale, which measures the time and extent to which physical or emotional health interferes with social activities.23

Chang and colleagues,25 using the SF-36, the quality of well-being (QWB) instrument, the chronic respiratory questionnaire (CRQ), and the SGRQ, showed that 50 patients with moderate pulmonary restriction from interstitial lung disease (ILD), including 33 patients with IPF, had impaired HRQL. Like the subjects in the studies by Martinez et al24 and De Vries et al,16 the domains concerning physical health and physical activity were most negatively impacted. For example, on the SF-36 the score on the role-physical subscale was lowest and most disparate from adult norms in the United States. At least half of the cohort scored this subscale at its lowest possible value, zero. Also, according to the SF-36, general health and vitality (ie, energy/pep) were among the most impaired HRQL domains. The mental health of this cohort, as evaluated by the SF-36 mental component summary (which is the aggregate of the vitality, social functioning, role-emotional, and mental health domains), was similar to that experienced by a large sample of US adults from the general population.

As with the SF-36, according to the SGRQ the HRQL of the ILD patients in the study by Chang et al25 was most impaired in physical activities. Approximately 50% of the patients in that study had activity subscale scores in the moderately impaired range (ie, between 40 and 73). This degree of impairment in physical activities (that either cause or are limited by breathlessness) is very similar to that observed in the 10 patients in the IPF focus groups in the study by DeVries et al,,14 and also in 375 subjects with moderate COPD from another study. Compared to the 750 healthy control subjects from that same study, IPF and COPD patients have markedly worse HRQL in terms of physical activity.2627

For the patients in the study by Chang et al,25 as measured by the CRQ, dyspnea and fatigue (specifically, energy levels and how frequently respondents “feel sluggish”) were substantially more impaired than their emotional function or mastery over their disease. Like the SGRQ, the CRQ is a respiratory-specific HRQL instrument that was developed for patients with “chronic airflow limitation.”28 It includes 20 items grouped into four domains, but, unlike the SGRQ, lower scores indicate worse HRQL. The original CRQ is interviewer administered, and its dyspnea domain allows patients to volunteer, or choose from a list, their five most important daily activities that are affected by breathlessness on which to base their responses.

In the study by Chang et al,25 the scores of the cohort on the QWB instrument were also low. The QWB is a multiattribute health state instrument, and its lone score also represents a summary metric for HRQL.29 To complete the scale, a respondent affirms items identifying her current health state (eg, blindness or severely impaired vision in both eyes, excessive worry or anxiety in the last 3 days, or use of an oxygen tank). Value weights (derived during the development of the QWB) for affirmed items are summed and subtracted from 1 (the score corresponding to asymptomatic full function). The more features that are present, the greater the sum of their weights and the further the QWB score (ie, HRQL) decreases from 1.

In the study by Chang et al,25 the median QWB score was 0.635. In comparison, a hypothetical 68-year-old patient with shortness of breath, who remains in a bed or chair for most of the day but is able to perform self-care and drive a car, has a QWB score of 0.605. If he were able to remain out of a bed or chair for most of the day, his score would increase to 0.682.30

Disease Severity Measures and HRQL or QOL: Concurrent Validity

In IPF patients, some scores for the measurement instruments discussed above correlate significantly with certain measures of disease severity. Studies have examined associations between HRQL (or QOL) scores and pulmonary function test results, 6-min walk distance, measures of oxygenation, and breathlessness assessed using several dyspnea instruments.

In general, the results of pulmonary function testing (eg, FVC, total lung capacity [TLC], and Dlco) correlate with HRQL scores, but many of the correlations are not statistically significant and are not strong (Table 3 ). Although it was only assessed in one study, the 6-min walk distance appears to be more strongly correlated with HRQL than FVC, TLC, or Dlco. In one study,18 resting arterial blood pH correlated highly and significantly with physical activity (as assessed by the physical functioning subscale of the SF-36). In most other cases, correlations between HRQL and data from resting arterial blood gas measurements were neither strong nor significant. Clark et al31 used multivariable linear regression to show significant associations between nocturnal oxygen saturation and HRQL in patients with IPF.

Across the four studies16,18,2425 that examined it, dyspnea correlated better with HRQL and QOL than any other disease symptom or clinical severity measure. Many of the strongest correlations occurred between dyspnea and subscales assessing aspects of physical health (eg, the SF-36 physical component summary, physical functioning subscale, and vitality subscale).

In summary, in patients with IPF, scores from certain HRQL and QOL instruments correlate in the expected direction with several clinically important measures of disease severity, symptoms, and functional status. With the exception of the association between dyspnea and HRQL/QOL, in particular, domains that assess aspects of physical health and dyspnea, these correlations are not strong. This may suggest that clinical disease severity measures are poor predictors of HRQL and QOL. At the same time, the weak-to-moderately significant correlations may suggest that the instruments provide information about IPF patients that is unique from that generated by the other disease severity measures.

While the handful of studies assessing HRQL and QOL have shed light on some of the difficulties encountered by IPF patients, important questions remain. For example, what is the impact of supplemental oxygen use and drug therapy on HRQL and QOL? Are the existing HRQL instruments really appropriate for assessing patients with IPF? Are there important features of this disease, as it affects aspects of HRQL, that are not well-assessed by the existing instruments? What are the strongest predictors of HRQL? How does HRQL change over time?

Potential Barriers to Generalization of Prior Studies

Before setting out to fill the gaps, we must consider what is known about QOL in IPF patients and determine whether the studies examining HRQL and QOL in these patients have externally valid results.

A key aspect of generalizing the results of prior studies is confirming that the study population is itself representative of patients in the general population. For IPF, this means verifying that investigators used a meaningful case definition for the inclusion of study participants. Some of the studies assessing HRQL and QOL in IPF patients used case definitions for IPF that are different from the one currently endorsed by the American Thoracic Society/European Respiratory Society. Other studies did not report a case definition at all.

For their study, Chang et al25 expanded the definition of IPF to include subjects with a nonspecific interstitial pneumonia (NSIP) pattern of lung injury seen on biopsy specimens. Presumably, pathologic specimens for some of the 24 patients who underwent biopsy showed an NSIP pattern, which would confer a diagnosis of NSIP (NSIP disease) on them, and not a diagnosis of IPF. Prior to analyzing subjects with NSIP and IPF as a homogeneous group, it would be important to know whether and how their HRQL scores differ. It would also be important to know whether the two groups had differences in pulmonary function (ie, disease severity) that would help to explain putative differences in HRQL. Because the investigators did not report the number of NSIP patients or their pulmonary function, the influence of these patients on the direction and magnitude of the HRQL scores of IPF patients is unknown, and generalizing their mean instrument scores to the general IPF population, which, as currently defined, does not include patients with NSIP, should be done with caution.

Issues related to instrument administration can also introduce bias and raise questions about the generalizability of a study. For example, in the study by Martinez et al,18 participants’ impaired reading abilities forced the investigators to administer the SF-36 with the aid of an interviewer who was not blinded to the disease status of the study subjects. Although the interviewers took care to maintain impartiality, they could have biased scores by unknowingly clarifying questions or emphasizing words differently to one of the groups.

The Impact of Supplemental Oxygen Use on HRQL or QOL

According to the study by Chang et al,25 the users of supplemental oxygen had lower HRQL scores on all four instruments (ie, CRQ, SGRQ, QWB, and SF-36) than nonusers. Surprisingly, in the study by De Vries and colleagues,,16 there was no difference in QOL, as assessed by the WHOQOL-100, between IPF subjects using supplemental oxygen (n = 14) and subjects not using supplemental oxygen (n = 27). Subscale scores were not reported, so it is unclear whether this lack of a significant difference was seen in the level of independence subscale. Because this subscale includes items that assess dependence on medicinal substances or medical aids, one could imagine a significant difference in the score for oxygen users and nonusers on this subscale.

The Impact of Drug Therapy on HRQL or QOL

Conventional therapies for IPF have a number of potential side effects, and while taking prednisone most IPF patients experience at least one.4 Immunosuppressant medications often used in conjunction with, or in place of, prednisone require frequent laboratory monitoring and vigilance on the part of the administering clinicians for potential adverse effects. Despite this and the low likelihood of a beneficial response, most IPF patients take at least one of these medications in hope of any positive response.2,3233

The impact of these medications on HRQL and QOL has not been studied extensively. DeVries and colleagues found no difference in QOL between IPF subjects receiving steroids (n = 28) and IPF subjects not receiving steroids (n = 13) at the time of WHOQOL-100 administration.

Douglas and colleagues34administered the SF-36 at baseline and every 3 months to 26 IPF patients enrolled in their prospective randomized study of colchicine vs prednisone and found no difference in HRQL between the two groups (W. Douglas, MD; personal communication; May 2004). In the recent large, multicenter, randomized trial35 of interferon-γ1b for IPF patients, investigators found no difference in HRQL (assessed with the SGRQ) between the placebo and treatment groups after 48 weeks of therapy. For both of these studies, the lack of a significant change in HRQL scores suggests any of the following three very different possibilities: (1) the investigational drug truly had no effect on HRQL; (2) the study was not adequately powered to detect a significant change in HRQL; or (3) the instrument was not sensitive to a true change in HRQL.

The Appropriateness of Existing Instruments for Assessing HRQL in IPF

Investigators have noted problems with some of the existing instruments when they are applied to patients with IPF. For example, in the focus groups conducted by De Vries et al,14 participants raised concerns with the face validity of the SGRQ, including that it uses the terms “attack” or “attacks of chest trouble.” IPF patients did not think that these terms accurately characterized their disease experience.

Many items on the SGRQ have only “true” or “false” as response options, and patients objected to the absence of “sometimes” as a possible response option. Several participants retired before disease onset, making SGRQ items pertaining to work irrelevant. They also would have preferred items concerning supplemental oxygen use and its impact on QOL. Finally, IPF patients did not identify with the term “cough” alone, rather they described a “hacking” cough.

As part of their study, Chang and colleagues25 had their ILD patients rate the four instruments (CRQ, SGRQ, QWB, and SF-36) for relevance to patients with ILD. Although the patients rated all of the instruments equally high, the investigators encountered problems with the QWB and CRQ. All subjects’ QWB scores fell within a narrow range, and, regardless of the degree of pulmonary function impairment, subjects responded to questions pertaining to respiratory status similarly. Thus, the QWB failed to capture important differences in disease severity between subjects. For the CRQ (the original nonstandardized version), subjects with the most severe dyspnea simply chose less taxing physical activities to rate breathlessness, producing biased scores and deflating the perceived impact of dyspnea.

To guide researchers in their selection of study instruments, and to avoid some of these potential pitfalls, McHorney and Tarlov36 summarized instrument measurement standards and usefulness criteria. Besides being brief and easily administered, an instrument should have the following characteristics: (1) minimal floor and ceiling effects; (2) cross-sectional measurement precision (ie, acceptable internal consistency reliability [see the “Appendix” for definition] and known standard errors of measurement); (3) longitudinal monitoring measurement precision (eg, test-retest reliability and a reliable change index); and (4) validity and sensitivity to clinical change for both the population and the purpose for which it is to be used. By these criteria, most of the instruments used in the studies discussed above have established track records for populations and diseases other than IPF. For patients with IPF, we have much to learn about the usefulness of these instruments.

Whether for an existing instrument or for a newly developed IPF-specific HRQL instrument, the need to determine floor and ceiling effect levels, to perform assessments of reliability, to evaluate sensitivity to change in HRQL (also called responsiveness), and to establish predictive and concurrent validity create opportunities for research. To date, the studies designed to validate HRQL (or QOL) instruments in patients with IPF have used only the approach of establishing concurrent validity.

Floor and Ceiling Effect Levels

Instruments convey less useful information when high numbers of respondents score at the extremes. When a respondent’s total instrument or subscale score is at the highest or lowest possible value, it is unknown whether the patient would have chosen a more extreme option had one been available. For example, suppose that a subject’s baseline HRQL score in a drug trial is 10, which is the maximum value for the instrument being used. After 6 weeks of treatment with the experimental drug, the patient’s HRQL has improved substantially. However, because there is no room for her score to increase, her score on the instrument would again be 10. The instrument has imposed a ceiling effect, which has prevented it from detecting the improvement. Such a limitation imposed at the minimum score is known as a floor effect. By reporting the percentage of subjects who are receiving the maximum and minimum scores, investigators provide an estimate of the degree of the potential limiting impacts of ceiling and floor effects.

Besides altering the accuracy of the scores of an instrument, floor and ceiling effects detract from the discriminant value, reliability, and responsiveness of an instrument. Similar detrimental effects occur when the “steps” between adjacent scores for an instrument are too large to reflect clinically meaningful changes in specific patient populations. This is a potential problem with many generic instruments, and it occurred with the QWB in the study by Chang et al.25

An IPF-Specific HRQL Instrument

An instrument may have strong reliability and validity for its intended uses in a broad, general population, but poor reliability and validity in the patient population of interest. By focusing on aspects of particular relevance to patients with one disease, disease-specific instruments decrease the size of the steps between adjacent scores and usually display better discriminant value, reliability, validity, and responsiveness than generic instruments administered in that population. A carefully developed, psychometrically sound, IPF-specific HRQL instrument would be expected to outperform existing instruments and would be a significant contribution to patient-assessed outcomes research in IPF.

Based on published studies and our own preliminary research, such an instrument might include domains such as physical activity, stamina/energy, cough, ease of breathing/breathlessness, independence, emotional health, using/transporting supplemental O2, relations with/concerns about family members, anticipation of disease progression, financial security, travel, and end-of-life issues.

Assessments of Reliability

Like validity, instrument reliability is relative to the population in which the instrument is used.12 Thus, reliability coefficients should be determined whenever an instrument is used in a new population. This ensures that the instrument is performing at an acceptable level and allows comparisons of its performance in the new population with its historical performance (eg, in the population for which it was developed). Reasonable minimal instrument reliability requirements include an internal consistency reliability > 0.8 and a test-retest reliability of > 0.5.

Assessments of Sensitivity to Change in Longitudinal Studies

Longitudinal assessments of HRQL in IPF patients have yet to be performed, and without these studies, we remain uncertain about an instrument’s ability to accurately and reliably detect changes in HRQL in this population. It is only through longitudinal comparisons that we can determine the instruments that are best suited for this evaluative function. By observing HRQL over time, we expand our understanding of the disease process and its impact on patients. Thus, through longitudinal studies we can assess HRQL in relation to disease progression and highlight the domains that receive the most negative impact and are most in need of intervention.

Longitudinal studies also provide a platform for evaluating how IPF patients adapt to disease. Adaptation, also referred to as a response shift,3738 occurs when the meaning of an individual’s assessment of a given construct (eg, the HRQL) changes. Response shifts in HRQL may occur for any of the following three reasons: (1) a respondent’s internal measurement standards change (ie, the patient internally recalibrates the measurement scale to accommodate increased disability, resulting in a score suggesting better HRQL than that which might be supposed); (2) a respondent entirely reconceptualizes or redefines what HRQL means to himself; or (3) the value or importance that a respondent places on one or more HRQL component domains changes. The phenomenon of adaptation likely occurs in patients with IPF, however, identifying the frequency, extent, and domains in which it occurs, as well as the patient characteristics that may determine whether it occurs, requires further investigation.

A longitudinal study would be a valuable contribution to HRQL research in IPF patients. Without such studies, we are left with several questions. Are we measuring the right thing with our instruments? Are our interventions in some way benefiting these patients, but we are using the wrong measures to detect that benefit? Or are we not benefiting and possibly even impairing patients’ HRQL with our interventions without knowing it?

HRQL is impaired in many facets in patients with IPF, but domains concerning physical health and physical well-being are the most profoundly impacted, insofar as HRQL is appropriately measured by the currently available instruments. However, our ability to draw confident conclusions is impaired by the fact that only a handful of studies has examined HRQL in IPF patients. Their small sample sizes, variable case inclusion criteria, and other issues related to study design and instrument administration warrant caution before generalizing their results. The existing HRQL instruments have been studied only in limited contexts. Thus, there is much to learn about their potential roles in assessing IPF patients. A major focus of future research should be the inclusion of HRQL as a study end point to ensure that any small gains potentially observed in survival are not accompanied by unacceptable decrements in HRQL. Other important opportunities include determining the floor and ceiling effects, the reliability, and the validity of existing or perhaps a newly developed and more suitable IPF-specific HRQL instrument. Expanding the circumstances under which the evaluation of these instruments takes place, in particular to include longitudinal studies of HRQL, will help investigators to choose the most appropriate instruments for their studies and to advance the knowledge of an important and highly patient-valued aspect of this disease.

Definitions of Some Key Terms

Construct: some intangible thing (eg, HRQL) intended to be measured.

Item: a statement or question devised to assess a particular construct.

Instrument: a collection of related items intended to measure the same construct.

Domain: a small group of closely related items (within the larger instrument) that assess a specific attribute or dimension (eg, physical activity) of the broader construct (eg, HRQL) being measured by the instrument.

Subscale: in the context of an instrument’s scores, a subscale refers to the items within a single domain, or perhaps from a small set of closely related domains.

Internal consistency reliability: an index of the interrelatedness of items comprising an instrument; a measure of the extent to which the items in an instrument measure the same construct.12,38

Test-retest reliability: the correlation between a stable individual’s scores that result from the administration of an instrument on two separate occasions (an instrument with good test-retest reliability captures true differences in scores between the different time points with minimal or no introduction of measurement error).

Evaluative: the function an instrument possesses that refers to its sensitivity to changes in HRQL over time within individual patients.39

Discriminative: the function an instrument possesses that refers to its ability to measure differences in HRQL between patients (eg, patients with different diseases), a function sometimes referred to as discriminative.40

Abbreviations: CRQ = chronic respiratory questionnaire; Dlco = diffusing capacity of the lung for carbon monoxide; HRQL = health-related quality of life; ILD = interstitial lung disease; IPF = idiopathic pulmonary fibrosis; NSIP = nonspecific interstitial pneumonia; QOL = quality of life; QWB = quality of well-being; SF-36 = Medical Outcomes Study 36-item short form; SGRQ = St. George Respiratory Questionnaire; TLC = total lung capacity; WHO = World Health Organization; WHOQOL-100 = World Health Organization quality of life assessment 100-item instrument

Dr. Swigris received support from a National Institutes of Health training grant (T32 HL07948–01A1). Dr. Gould received an Advanced Research Career Development Award from the Veterans Affairs Health Services Research and Development Service.

The views expressed in this article are those of the authors and not necessarily the views of the Department of Veterans Affairs.

Table Graphic Jump Location
Table 1. Measurement Instrument Validation Studies in Patients With IPF
Table Graphic Jump Location
Table 2. Instruments Used in Validation Studies in IPF Patients*
* 

ADL = activity of daily living.

Table Graphic Jump Location
Table 3. Correlation Coefficients for Associations Between HRQL (and QOL) Instrument Scores and Measures of IPF Severity*
* 

Spo2 = pulse oximetric saturation; NR = not reported.

 

Statistically significant correlation coefficient.

 

Mean value of two statistically significant correlation coefficients assessing the same association but in separate studies.

§ 

Parameters assessed by investigators but not reported due to lack of statistical significance.

The authors thank J. Randall Curtis, MD, MPH, for his thoughtful input and critique of a previous version of this manuscript.

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American Thoracic Society and the European Respiratory Society. Idiopathic pulmonary fibrosis: diagnosis and treatment; International consensus statement—American Thoracic Society (ATS), and the European Respiratory Society (ERS).Am J Respir Crit Care Med2000;161,646-664. [PubMed]
 
Panos, RJ, Mortenson, RL, Niccoli, SA, et al Clinical deterioration in patients with idiopathic pulmonary fibrosis: causes and assessment.Am J Med1990;88,396-404. [CrossRef] [PubMed]
 
Flaherty, KR, Toews, GB, Lynch, JP, III, et al Steroids in idiopathic pulmonary fibrosis: a prospective assessment of adverse reactions, response to therapy, and survival.Am J Med2001;110,278-282. [CrossRef] [PubMed]
 
Curtis, J, Martin, D, Martin, T Patient-assessed health outcomes in chronic lung disease: what are they, how do they help us, and where do we go from here?Am J Respir Crit Care Med1997;156,1032-1039. [PubMed]
 
Flanagan, J A research approach to improving our quality of life.Am Psychol1978;33,138-147. [CrossRef]
 
Oleson, M Subjectively perceived quality of life.Image (IN)1990;22,187-190
 
American Thoracic Society. Quality of life resource. Available at: www.atsqol.org. Accessed March 1, 2004.
 
Organization, WH. Constitution of the World Health Organization: Chronicle of the World Health Organization 1. 1947; World Health Organization. Geneva, Switzerland:.
 
Testa, M, Simonson, D Current concepts: assessment of quality-of-life outcomes.N Engl J Med1996;334,835-840. [CrossRef] [PubMed]
 
Landy, F Stamp collecting versus science.Am Psychol1986;41,1183-1192. [CrossRef]
 
Streiner, D, Norman, G. Health measurement scales: a practical guide to their development and use. 1995; Oxford University Press. New York:.
 
Curtis, J, Deyo, R, Hudson, L Health-related quality of life among patients with chronic obstructive pulmonary disease.Thorax1994;49,162-170. [CrossRef] [PubMed]
 
De Vries, J, Seebregts, A, Drent, M Assessing health status and quality of life in idiopathic pulmonary fibrosis: which measure should be used?Respir Med2000;94,273-278. [CrossRef] [PubMed]
 
Jones, P, Quirk, F, Baveystock, C The St. George’s Respiratory Questionnaire.Respir Med1991;85,25-31. [CrossRef] [PubMed]
 
De Vries, J, Kessels, B, Drent, M Quality of life of idiopathic pulmonary fibrosis patients.Eur Respir J2001;17,954-961. [CrossRef] [PubMed]
 
Group, TW The world health organization quality of life assessment (WHOQOL): development and general psychometric properties.Soc Sci Med1998;46,1569-1585. [CrossRef] [PubMed]
 
Martinez, T, Pereira, C, dos Santos, M, et al Evaluation of the short-form 36-item questionnaire to measure health-related quality of life in patients with idiopathic pulmonary fibrosis.Chest2000;117,1627-1632. [CrossRef] [PubMed]
 
Ware, JE, Jr, Sherbourne, C The MOS 36-item short-form health survey (SF-36): I. Conceptual framework and item selection.Med Care1992;30,473-483. [CrossRef] [PubMed]
 
Ware, JE, Jr SF-36 health survey update.Spine2000;25,3130-3139. [CrossRef] [PubMed]
 
McHorney, C, Ware, JE, Jr, Lu, J, et al The MOS 36-item Short Form Health Survey (SF-36): III. Tests of data quality, scaling assumptions, and reliability across diverse patient groups.Med Care1994;32,40-66. [CrossRef] [PubMed]
 
Bousquet, J, Knani, J, Dhivert, H, et al Quality of life in asthma: I. Internal consistency and validity of the SF-36 questionnaire.Am J Respir Crit Care Med1994;149,371-375. [PubMed]
 
McHorney, C, Ware, JE, Jr, Raczek, A The MOS 36-item short-form health survey (SF-36): II. Psychometric and clinical tests of validity in measuring physical and mental health constructs.Med Care1993;31,247-263. [CrossRef] [PubMed]
 
Martinez, J, Martinez, T, Galhardo, F, et al Dyspnea scales as a measure of health-related quality of life in patients with idiopathic pulmonary fibrosis.Med Sci Monit2002;8,CR405-CR410. [PubMed]
 
Chang, J, Curtis, R, Patrick, D, et al Assessment of health-related quality of life in patients with interstitial lung disease.Chest1999;116,1175-1182. [CrossRef] [PubMed]
 
Spencer, S, Calverley, P, Burge, P, et al Health status deterioration in patients with chronic obstructive pulmonary disease.Am J Respir Crit Care Med2001;163,122-128. [PubMed]
 
Burge, P, Calverley, P, Jones, P, et al Randomized, double-blind, placebo controlled study of fluticasone proprionate in patients with moderate to severe chronic obstructive pulmonary disease: the ISOLDE trial.BMJ2000;320,1297-1303. [CrossRef] [PubMed]
 
Guyatt, G, Berman, L, Townsend, M, et al A measure of quality of life for clinical trials of chronic lung disease.Thorax1987;42,773-778. [CrossRef] [PubMed]
 
Kaplan, R, Bush, J, Berry, C Health status: types of validity and the index of well-being.Health Serv Res1976;11,478-507. [PubMed]
 
Kaplan, R, Bush, J Health-related quality of life measurement for evaluation research and policy analysis.Health Psychol1982;1,61-81. [CrossRef]
 
Clark, M, Cooper, B, Singh, S, et al A survey of nocturnal hypoxaemia and health related quality of life in patients with cryptogenic fibrosing alveolitis.Thorax2001;56,482-486. [CrossRef] [PubMed]
 
Johnston, ID, Gomm, S, Kalra, A The management of cryptogenic fibrosing alveolitis in three regions of the United Kingdom.Eur Respir J1993;6,891-893. [PubMed]
 
Douglas, WW, Ryu, JH, Schroeder, DR Idiopathic pulmonary fibrosis: impact of oxygen and colchicine, prednisone, or no therapy on survival.Am J Respir Crit Care Med2000;161,1172-1178. [PubMed]
 
Douglas, WW, Ryu, JH, Bjoraker, JA, et al Colchicine versus prednisone as treatment of usual interstitial pneumonia.Mayo Clin Proc1997;72,201-209. [CrossRef] [PubMed]
 
Raghu, G, Brown, KK, Bradford, WZ, et al A placebo-controlled trial of interferonγ-1b in patients with idiopathic pulmonary fibrosis.N Engl J Med2004;350,125-133. [CrossRef] [PubMed]
 
McHorney, C, Tarlov, A Individual-patient monitoring in clinical practice: are available health status surveys adequate?Qual Life Res1995;4,293-307. [CrossRef] [PubMed]
 
Howard, G, Dailey, P Response shift bias: a source of contamination of self-report measures.J Appl Psychol1979;64,144-150. [CrossRef]
 
Golembiewski, R, Billingsley, K, Yeager, S Measuring change and persistence in human affairs: types of change generated by old designs.J Appl Behav Sci1976;12,133-157. [CrossRef]
 
Veterans Administration Health Services Research and Development Service. Measurement excellence initiative (MEI). Available at: www.measurementexperts.org. Accessed March 1, 2004.
 
Guyatt, G, Feeny, D, Patrick, D Measuring health-related quality of life.Ann Intern Med1993;118,622-629. [PubMed]
 

Figures

Tables

Table Graphic Jump Location
Table 1. Measurement Instrument Validation Studies in Patients With IPF
Table Graphic Jump Location
Table 2. Instruments Used in Validation Studies in IPF Patients*
* 

ADL = activity of daily living.

Table Graphic Jump Location
Table 3. Correlation Coefficients for Associations Between HRQL (and QOL) Instrument Scores and Measures of IPF Severity*
* 

Spo2 = pulse oximetric saturation; NR = not reported.

 

Statistically significant correlation coefficient.

 

Mean value of two statistically significant correlation coefficients assessing the same association but in separate studies.

§ 

Parameters assessed by investigators but not reported due to lack of statistical significance.

References

Coultas, D, Zumwalt, R, Black, W, et al (1994) The epidemiology of interstitial lung disease.Am J Respir Crit Care Med150,967-972. [PubMed]
 
American Thoracic Society and the European Respiratory Society. Idiopathic pulmonary fibrosis: diagnosis and treatment; International consensus statement—American Thoracic Society (ATS), and the European Respiratory Society (ERS).Am J Respir Crit Care Med2000;161,646-664. [PubMed]
 
Panos, RJ, Mortenson, RL, Niccoli, SA, et al Clinical deterioration in patients with idiopathic pulmonary fibrosis: causes and assessment.Am J Med1990;88,396-404. [CrossRef] [PubMed]
 
Flaherty, KR, Toews, GB, Lynch, JP, III, et al Steroids in idiopathic pulmonary fibrosis: a prospective assessment of adverse reactions, response to therapy, and survival.Am J Med2001;110,278-282. [CrossRef] [PubMed]
 
Curtis, J, Martin, D, Martin, T Patient-assessed health outcomes in chronic lung disease: what are they, how do they help us, and where do we go from here?Am J Respir Crit Care Med1997;156,1032-1039. [PubMed]
 
Flanagan, J A research approach to improving our quality of life.Am Psychol1978;33,138-147. [CrossRef]
 
Oleson, M Subjectively perceived quality of life.Image (IN)1990;22,187-190
 
American Thoracic Society. Quality of life resource. Available at: www.atsqol.org. Accessed March 1, 2004.
 
Organization, WH. Constitution of the World Health Organization: Chronicle of the World Health Organization 1. 1947; World Health Organization. Geneva, Switzerland:.
 
Testa, M, Simonson, D Current concepts: assessment of quality-of-life outcomes.N Engl J Med1996;334,835-840. [CrossRef] [PubMed]
 
Landy, F Stamp collecting versus science.Am Psychol1986;41,1183-1192. [CrossRef]
 
Streiner, D, Norman, G. Health measurement scales: a practical guide to their development and use. 1995; Oxford University Press. New York:.
 
Curtis, J, Deyo, R, Hudson, L Health-related quality of life among patients with chronic obstructive pulmonary disease.Thorax1994;49,162-170. [CrossRef] [PubMed]
 
De Vries, J, Seebregts, A, Drent, M Assessing health status and quality of life in idiopathic pulmonary fibrosis: which measure should be used?Respir Med2000;94,273-278. [CrossRef] [PubMed]
 
Jones, P, Quirk, F, Baveystock, C The St. George’s Respiratory Questionnaire.Respir Med1991;85,25-31. [CrossRef] [PubMed]
 
De Vries, J, Kessels, B, Drent, M Quality of life of idiopathic pulmonary fibrosis patients.Eur Respir J2001;17,954-961. [CrossRef] [PubMed]
 
Group, TW The world health organization quality of life assessment (WHOQOL): development and general psychometric properties.Soc Sci Med1998;46,1569-1585. [CrossRef] [PubMed]
 
Martinez, T, Pereira, C, dos Santos, M, et al Evaluation of the short-form 36-item questionnaire to measure health-related quality of life in patients with idiopathic pulmonary fibrosis.Chest2000;117,1627-1632. [CrossRef] [PubMed]
 
Ware, JE, Jr, Sherbourne, C The MOS 36-item short-form health survey (SF-36): I. Conceptual framework and item selection.Med Care1992;30,473-483. [CrossRef] [PubMed]
 
Ware, JE, Jr SF-36 health survey update.Spine2000;25,3130-3139. [CrossRef] [PubMed]
 
McHorney, C, Ware, JE, Jr, Lu, J, et al The MOS 36-item Short Form Health Survey (SF-36): III. Tests of data quality, scaling assumptions, and reliability across diverse patient groups.Med Care1994;32,40-66. [CrossRef] [PubMed]
 
Bousquet, J, Knani, J, Dhivert, H, et al Quality of life in asthma: I. Internal consistency and validity of the SF-36 questionnaire.Am J Respir Crit Care Med1994;149,371-375. [PubMed]
 
McHorney, C, Ware, JE, Jr, Raczek, A The MOS 36-item short-form health survey (SF-36): II. Psychometric and clinical tests of validity in measuring physical and mental health constructs.Med Care1993;31,247-263. [CrossRef] [PubMed]
 
Martinez, J, Martinez, T, Galhardo, F, et al Dyspnea scales as a measure of health-related quality of life in patients with idiopathic pulmonary fibrosis.Med Sci Monit2002;8,CR405-CR410. [PubMed]
 
Chang, J, Curtis, R, Patrick, D, et al Assessment of health-related quality of life in patients with interstitial lung disease.Chest1999;116,1175-1182. [CrossRef] [PubMed]
 
Spencer, S, Calverley, P, Burge, P, et al Health status deterioration in patients with chronic obstructive pulmonary disease.Am J Respir Crit Care Med2001;163,122-128. [PubMed]
 
Burge, P, Calverley, P, Jones, P, et al Randomized, double-blind, placebo controlled study of fluticasone proprionate in patients with moderate to severe chronic obstructive pulmonary disease: the ISOLDE trial.BMJ2000;320,1297-1303. [CrossRef] [PubMed]
 
Guyatt, G, Berman, L, Townsend, M, et al A measure of quality of life for clinical trials of chronic lung disease.Thorax1987;42,773-778. [CrossRef] [PubMed]
 
Kaplan, R, Bush, J, Berry, C Health status: types of validity and the index of well-being.Health Serv Res1976;11,478-507. [PubMed]
 
Kaplan, R, Bush, J Health-related quality of life measurement for evaluation research and policy analysis.Health Psychol1982;1,61-81. [CrossRef]
 
Clark, M, Cooper, B, Singh, S, et al A survey of nocturnal hypoxaemia and health related quality of life in patients with cryptogenic fibrosing alveolitis.Thorax2001;56,482-486. [CrossRef] [PubMed]
 
Johnston, ID, Gomm, S, Kalra, A The management of cryptogenic fibrosing alveolitis in three regions of the United Kingdom.Eur Respir J1993;6,891-893. [PubMed]
 
Douglas, WW, Ryu, JH, Schroeder, DR Idiopathic pulmonary fibrosis: impact of oxygen and colchicine, prednisone, or no therapy on survival.Am J Respir Crit Care Med2000;161,1172-1178. [PubMed]
 
Douglas, WW, Ryu, JH, Bjoraker, JA, et al Colchicine versus prednisone as treatment of usual interstitial pneumonia.Mayo Clin Proc1997;72,201-209. [CrossRef] [PubMed]
 
Raghu, G, Brown, KK, Bradford, WZ, et al A placebo-controlled trial of interferonγ-1b in patients with idiopathic pulmonary fibrosis.N Engl J Med2004;350,125-133. [CrossRef] [PubMed]
 
McHorney, C, Tarlov, A Individual-patient monitoring in clinical practice: are available health status surveys adequate?Qual Life Res1995;4,293-307. [CrossRef] [PubMed]
 
Howard, G, Dailey, P Response shift bias: a source of contamination of self-report measures.J Appl Psychol1979;64,144-150. [CrossRef]
 
Golembiewski, R, Billingsley, K, Yeager, S Measuring change and persistence in human affairs: types of change generated by old designs.J Appl Behav Sci1976;12,133-157. [CrossRef]
 
Veterans Administration Health Services Research and Development Service. Measurement excellence initiative (MEI). Available at: www.measurementexperts.org. Accessed March 1, 2004.
 
Guyatt, G, Feeny, D, Patrick, D Measuring health-related quality of life.Ann Intern Med1993;118,622-629. [PubMed]
 
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