Frederick S. Wamboldt

The SF-36 and SGRQ: validity and first look at minimum important differences in IPF

RATIONALEnHealth-related quality of life (HRQL) is an important outcome in drug trials. Little is known about how the Short Form-36 (SF-36) and Saint Georges Respiratory Questionnaire (SGRQ) perform in idiopathic pulmonary fibrosis (IPF).nnnOBJECTIVESnTo examine the validity of the SF-36 and SGRQ and to determine scores from each that would constitute a minimum important difference (MID).nnnMETHODSnWe analyzed data from a recently completed trial that enrolled subjects with well-defined IPF who completed the SF-36, SGRQ, and Baseline/Transition Dyspnea Index at baseline and six months. We compared mean changes in HRQL scores between groups of subjects whose disease severity changed over six months according to clinical anchors (FVC, DLCO, and dyspnea). We estimated the MID for each domain by using both anchor- and distribution-based approaches.nnnMAIN RESULTSnResults supported the validity of the SF-36 and SGRQ for use in longitudinal studies. Mean changes in domain scores differed significantly between subjects whose clinical status improved and those whose clinical status declined according to the anchors. MID estimates for the SF-36 ranged from 2-4 points and from 5-8 points for the SGRQ.nnnCONCLUSIONnIn IPF, the SF-36 and SGRQ possess reasonable validity for differentiating subjects whose disease severity changes over time. More studies are needed to continue the validation process, to refine estimates of the MIDs for the SF-36 or SGRQ, and to determine if a disease-specific instrument will perform better than either of these.

The 6 minute walk in idiopathic pulmonary fibrosis: longitudinal changes and minimum important difference

Rationale The response characteristics of the 6u2005minute walk test (6MWT) in studies of idiopathic pulmonary fibrosis (IPF) are only poorly understood, and the change in walk distance that constitutes the minimum important difference (MID) over time is unknown. Objectives To examine changes over time in distance walked (ie, 6MWD) during the 6MWT and to estimate the change in distance that constitutes the MID in patients with IPF. Methods Data from a recently completed trial that included subjects with IPF who completed the 6MWT, Saint Georges Respiratory Questionnaire (SGRQ) and forced vital capacity (FVC) at 6 and 12u2005 months were used to examine longitudinal changes in 6MWD. Both anchor- and distribution-based approaches as well as linear regression analyses were used to determine the MID for 6MWD. The SGRQ Total score and FVC were used as clinical anchors. Main results Among 123 subjects alive and able to complete the 6MWT at both follow-up time points, 6MWD did not change significantly over time (378.1u2005m at baseline vs 376.8u2005m at 6u2005months vs 361.3u2005m at 12u2005months, p=0.5). The point estimate for the 6MWD MID was 28u2005m with a range of 10.8–58.5u2005m. Conclusion In a group of patients with IPF with moderate physiological impairment, for those alive and able to complete a 6MWT, 6MWD does not change over 12 months. At the population level, the MID for 6MWD appears to be ∼28u2005m. Further investigation using other anchors and derivation methods is required to refine estimates of the MID for 6MWD in this patient population.

Management of Cardiac Sarcoidosis in the United States: A Delphi Study

BACKGROUNDnNo formal guidelines exist to guide physicians caring for patients with sarcoidosis in their screening for management of patients with cardiac sarcoidosis. We conducted a modified Delphi study to investigate if a consensus could be reached on the best approaches for screening for and management of cardiac sarcoidosis.nnnMETHODSnA modified Delphi study design with two rounds of questionnaires was used to investigate if a consensus existed among sarcoid experts in the United States on the best management approaches for cardiac sarcoidosis. Experts were identified based on their national reputation as sarcoid experts and by being actively involved in sarcoidosis clinics at their institutions.nnnRESULTSnOverall agreement was low to moderate. Agreement was reached on the role of history, physical examination, and 12-lead ECG in screening, echocardiogram, Holter monitor, myocardial fluorodeoxyglucose PET scan, and cardiac MRI in workup, and steroids in treatment. Agreement was not reached on the role of signal-averaged ECG in screening, optimum dose of prednisone, use of steroid-sparing agents, and duration of treatment. Several comments underscore the diverse approaches and uncertainty that exist in managing cardiac sarcoidosis.nnnCONCLUSIONSnOur study highlights the dilemma that sarcoid experts face in their approach to cardiac sarcoidosis. It also highlights the lack of agreement among sarcoid experts on key aspects of diagnosis and management and stresses the importance of collaborative efforts to investigate the best strategies for screening for and management of cardiac sarcoidosis.

Heart Rate Recovery After 6-Min Walk Test Predicts Survival in Patients With Idiopathic Pulmonary Fibrosis

BACKGROUNDnIn patients with idiopathic pulmonary fibrosis (IPF), our objectives were to identify predictors of abnormal heart rate recovery (HRR) at 1 min after completion of a 6-min walk test (6MWT) [HRR1] and 2 min after completion of a 6MWT (HRR2), and to determine whether abnormal HRR predicts mortality.nnnMETHODSnFrom 2003 to 2008, we identified IPF patients who had been evaluated at our center (n = 76) with a pulmonary physiologic examination and the 6MWT. We used logistic regression to identify predictors of abnormal HRR, the product-limit method to compare survival in the sample stratified on HRR, and Cox proportional hazards analysis to estimate the prognostic capability of abnormal HRR.nnnRESULTSnCutoff values were 13 beats for abnormal HRR1 and 22 beats for HRR2. In a multivariable model, predictors of abnormal HRR1 were diffusing capacity of the lung for carbon monoxide (odds ratio [OR], 0.4 per 10% predicted; 95% confidence interval [CI], 0.2 to 0.7; p = 0.003), change in heart rate from baseline to maximum (OR, 0.9; 95% CI, 0.8 to 0.97; p = 0.01), and having a right ventricular systolic pressure > 35 mm Hg as determined by transthoracic echocardiogram (OR, 12.7; 95% CI, 2.0 to 79.7; p = 0.01). Subjects with an abnormal HRR had significantly worse survival than subjects with a normal HRR (for HRR1, p = 0.0007 [log-rank test]; for HRR2, p = 0.03 [log-rank test]); these results held for the subgroup of 30 subjects without resting pulmonary hypertension (HRR1, p = 0.04 [log-rank test]). Among several candidate variables, abnormal HRR1 appeared to be the most potent predictor of mortality (hazard ratio, 5.2; 95% CI, 1.8 to 15.2; p = 0.004).nnnCONCLUSIONnAbnormal HRR after 6MWT predicts mortality in IPF patients. Research is needed to confirm these findings prospectively and to examine the mechanisms of HRR in IPF patients.

Pulmonary rehabilitation in idiopathic pulmonary fibrosis: A call for continued investigation

Idiopathic pulmonary fibrosis (IPF) is a devastating disease that afflicts patients with relentlessly progressive shortness of breath [Joint Statement of the American Thoracic Society and the European Respiratory Society. Idiopathic pulmonary fibrosis: diagnosis and treatment. Am J Respir Crit Care Med 2000;161:646-64(1)]. Despite nearly 30 years of intense investigation, effective therapy for IPF remains elusive; median survival rates have stubbornly remained less than five years from the time of diagnosis [Bjoraker JA, Ryu JH, Edwin MK, Meyers J, Tazelaar H, Schroeder D, et al. Prognostic significance of histopathologic subsets in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 1998;157:199-203(2), Flaherty KR, Thwaite E, Kazerooni EA, Gross B, Toews GB, Colby TV, et al. Radiological versus histological diagnosis in UIP and NSIP: survival implications. Thorax 2003;58:143-48(3)], and no medical therapy has been proved to be in any way effective for the treatment of this disease. Without medications that help IPF patients live longer, an important question to ask is whether there are interventions that might allow these people to live better-to be more active; to experience less dyspnea, less depression, less anxiety; to possess a greater sense of control over their disease; and to have better quality of life. Pulmonary rehabilitation helps to accomplish many of these goals in patients with chronic obstructive pulmonary disease, and emerging data suggest that it may do the same for patients with IPF.

Benefits of pulmonary rehabilitation in idiopathic pulmonary fibrosis.

BACKGROUND: Information on the benefits of pulmonary rehabilitation (PR) in patients with idiopathic pulmonary fibrosis (IPF) is growing, but PRs effects on certain important outcomes is lacking. METHODS: We conducted a pilot study of PR in IPF and analyzed changes in functional capacity, fatigue, anxiety, depression, sleep, and health status from baseline to after completion of a standard, 6-week PR program. RESULTS: Six-min walk distance improved a mean ± standard error 202 ± 135 feet (P = .01) from baseline. Fatigue Severity Scale score also improved significantly, declining an average 1.5 ± 0.5 points from baseline. There were trends toward improvement in anxiety, depression, and health status. CONCLUSIONS: PR improves functional capacity and fatigue in patients with IPF. (ClinicalTrials.gov registration NCT00692796.)

Development of the ATAQ-IPF: a tool to assess quality of life in IPF.

BackgroundThere is no disease-specific instrument to assess health-related quality of life (HRQL) in patients with idiopathic pulmonary fibrosis (IPF).MethodsPatients perspectives were collected to develop domains and items for an IPF-specific HRQL instrument. We used item variance and Rasch analysis to construct the ATAQ-IPF (A Tool to Assess Quality of life in IPF).ResultsThe ATAQ-IPF version 1 is composed of 74 items comprising 13 domains. All items fit the Rasch model. Domains and the total instrument possess acceptable psychometric characteristics for a multidimensional questionnaire. The pattern of correlations between ATAQ-IPF scores and physiologic variables known to be important in IPF, along with significant differences in ATAQ-IPF scores between subjects using versus those not using supplemental oxygen, support its validity.ConclusionsPatient-centered and careful statistical methodologies were used to construct the ATAQ-IPF version 1, an IPF-specific HRQL instrument. Simple summation scoring is used to derive individual domain scores as well as a total score. Results support the validity of the ATAQ-IPF, and future studies will build on that validity.

A comparison of two spirituality instruments and their relationship with depression and quality of life in chronic heart failure.

Spirituality is a multifaceted construct related to health outcomes that remains ill defined and difficult to measure. Spirituality in patients with advanced chronic illnesses, such as chronic heart failure, has received limited attention. We compared two widely used spirituality instruments, the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being (FACIT-Sp) and the Ironson-Woods Spirituality/Religiousness Index (IW), to better understand what they measure in 60 outpatients with chronic heart failure. We examined how these instruments related to each other and to measures of depression and quality of life using correlations and principal component analyses. The FACIT-Sp measured aspects of spirituality related to feelings of peace and coping, whereas the IW measured beliefs, coping, and relational aspects of spirituality. Only the FACIT-Sp Meaning/Peace subscale consistently correlated with depression (r=-0.50, P<0.0001) and quality of life (r=0.41, P=0.001). Three items from the depression measure loaded onto the same factor as the FACIT-Sp Meaning/Peace subscale (r=0.43, -0.43, and 0.71), whereas the remaining 12 items formed a separate factor (Cronbachs alpha=0.82) when combined with the spirituality instruments in a principal component analysis. The results demonstrate several clinically useful constructs of spirituality in patients with heart failure and suggest that psychological and spiritual well-being, despite some overlap, remain distinct phenomena.

Pragmatic Trial of Health Care Technologies to Improve Adherence to Pediatric Asthma Treatment: A Randomized Clinical Trial

IMPORTANCEnMost patients with asthma take fewer than half of prescribed doses of controller medication. Interventions to improve adherence have typically been costly, impractical, and at best only minimally successful.nnnOBJECTIVEnTo test a speech recognition (SR) intervention to improve adherence to pediatric asthma controller medication.nnnDESIGN, SETTING, AND PARTICIPANTSnThe Breathe Well study was a 24-month pragmatic randomized clinical trial. The study was conducted within Kaiser Permanente Colorado, a large, group-model health maintenance organization. A total of 1187 children aged 3 to 12 years with a persistent asthma diagnosis and prescription for an inhaled corticosteroid were randomized to the computerized SR intervention or usual care condition and followed up for 24 months between October 2009 and February 2013.nnnINTERVENTIONSnSpeech recognition telephone calls to parents in the intervention condition were triggered when an inhaled corticosteroid refill was due or overdue. Calls were automatically tailored with medical and demographic information from the electronic health record and from parent answers to questions in the call regarding recent refills or a desire to receive help refilling, learn more about asthma control, or speak with an asthma nurse or pharmacy staff member.nnnMAIN OUTCOMES AND MEASURESnAdherence to pediatric asthma controller medication, measured as the medication possession ratio over 24 months.nnnRESULTSnIn the intention-to-treat analysis, inhaled corticosteroid adherence was 25.4% higher in the intervention group than in the usual care group (24-month mean [SE] adherence, 44.5% [1.2%] vs 35.5% [1.1%], respectively; Pu2009<u2009.001). Asthma-related urgent care events did not differ between the 2 groups. The intervention effect was consistent in subgroups stratified by age, sex, race/ethnicity, body mass index, and disease-related characteristics.nnnCONCLUSIONS AND RELEVANCEnThe interventions significant impact on adherence demonstrates strong potential for low-cost SR adherence programs integrated with an electronic health record. The absence of change in urgent care visits may be attributable to the already low number of asthma urgent care visits within Kaiser Permanente Colorado. Application of electronic health record-leveraged SR interventions may reduce health care utilization when applied in a population with less-controlled asthma.nnnTRIAL REGISTRATIONnclinicaltrials.gov Identifier: NCT00958932.

Brief-interval telephone surveys of medication adherence and asthma symptoms in the Childhood Asthma Management Program Continuation Study

BACKGROUNDnAlthough it is known that most patients do not consistently take controller medications every day, the impact of nonadherence on asthma control is not well documented.nnnOBJECTIVEnTo establish the relationship between medication adherence and symptom control in adolescents and young adults with asthma.nnnMETHODSnA total of 756 adolescents and young adults diagnosed as having mild to moderate asthma on entry into the original study underwent 6 monthly telephone interviews as an ancillary project to the Childhood Asthma Management Program Continuation Study. Participants were queried about medication use and symptom control within each 1-month interview window. Strategies adopted to improve self-report accuracy included use of repeated interviews, confidential reporting to staff unknown to the participants, and use of questions focused on recent behavior.nnnRESULTSnOnly participants who were consistently on inhaled corticosteroids (ICSs) for the entire 6-month study interval were included. Three groups of patients were contrasted: those not on ICSs (n = 420), those on ICSs with high adherence (> or = 75% of medication taken, n = 90), and those on ICSs with low/medium adherence (< 75% of medication taken, n = 148). Participants in the low/medium adherence group reported, on average, less symptom control and more variability in wheezing, awakening at night, missed activities, and beta2-agonist use during the 6-month period, although most in this group perceived their asthma to be under good control.nnnCONCLUSIONnDespite extensive patient education and support, diminished ICS adherence was frequent and undermined symptom control in this group of adolescents and young adults with mild to moderate asthma.