Sam Norton - University of Hertfordshire
University of Hertfordshire
Publications Authored By Sam Norton
Use by illness population, country, language and study design. The questionnaire's concurrent validity, predictive validity, sensitivity to change, discriminant validity and mean scores for different populations were summarised.
The review included 188 papers. The Brief IPQ has been administered to patients from age 8 to over 80, with a wide range of illnesses, in 26 languages from 36 countries. Pooled correlations between illness perceptions and depression, anxiety, blood glucose levels and quality of life were consistent with previous research and theory (range .25-.49 for consequences, identity and emotional representations; -.12 to -.27 for personal control). All items were able to predict some outcomes up to one-year follow-up. Each subscale demonstrated sensitivity to change after intervention in randomised controlled trials with the personal control and causal items showing most frequent change.
The Brief IPQ is widely used and has good psychometric properties. More studies should include and analyse the causal item.
In a cluster randomised controlled trial, 91 patients either self-affirmed or completed a matched control task before reading about the health-risks associated with inadequate fluid control.
Patients' perceptions of the health-risk information, intention and self-efficacy to control fluid were assessed immediately after presentation of health-risk information. Interdialytic weight gain (IDWG), excess fluid removed during haemodialysis, is a clinical measure of fluid treatment adherence. IDWG data were collected up to 12 months post-intervention.
Self-affirmed patients had significantly reduced IDWG levels over 12 months. However, contrary to predictions derived from self-affirmation theory, self-affirmed participants and controls did not differ in their evaluation of the health-risk information, intention to control fluid or self-efficacy.
A low-cost, high-reach health intervention based on self-affirmation theory was shown to reduce IDWG over a 12-month period, but the mechanism by which this apparent behaviour change occurred is uncertain. Further work is still required to identify mediators of the observed effects.
The EuroQoL (EQ-5D(TM)) indicated depression/anxiety symptom severity. Our primary outcomes of interest were (i) DAS-28 and (ii) physical disability measured via the HAQ. Secondary outcomes were: tender and swollen joint counts, patient global assessment, ESR and odds of reaching clinical remission. Multilevel models were used to assess the impact of baseline and persistent depression/anxiety on outcomes over 2 years.
Data from 379 patients were included. After adjusting for covariates, baseline depression/anxiety symptoms were associated with increased DAS-28 outcomes and increased tender joint counts. Persistent depression/anxiety symptoms were associated with increased DAS-28 scores, HAQ scores, tender joint counts and patient global assessment of disease activity, and reduced odds of reaching clinical remission. Patients with symptoms of depression/anxiety at baseline also showed a 50% reduction in prednisolone treatment effect, in comparison with patients with no symptoms of depression/anxiety at baseline.
Baseline and persistent symptoms of depression/anxiety are associated with poorer health outcomes over time, as well as reduced treatment response. Mental health should be routinely measured both in clinical practice and in research, and managed alongside rheumatological disease to optimize health outcomes. Further research is required to examine whether treatment of mental disorders can improve rheumatological outcomes.
To evaluate the psychometric properties of an 11-item fatigue severity measure, the Chalder Fatigue Questionnaire (CFQ) in MS including validity of the factor structure, internal reliability, discriminant validity and sensitivity to change.
Data were pooled from four previous studies investigating MS fatigue using the CFQ (n=444). Data analysis included confirmatory factor analysis to determine the factor structure and model fit, correlations to assess discriminant validity and effects sizes to determine sensitivity to change.
A bi-factor model with one general fatigue factor, incorporating two smaller group factors (mental and physical fatigue) had good model fit and appeared the most appropriate factor structure underlying the CFQ scale. The CFQ had high internal consistency, showed small to moderate correlations with impact of fatigue and mood, and was sensitive to change across low and high intensity behavioural interventions.
The CFQ measuring a composite of physical and mental fatigue severity (i.e. a total score) is a psychometrically sound measure of fatigue severity in MS.
Psychometric evaluation: three rounds of data collection from mental health service users (n = 92).
INSPIRE has two sub-scales. The 20-item Support sub-scale has convergent validity (0.60) and adequate sensitivity to change. Exploratory factor analysis (variance 71.4-85.1 %, Kaiser-Meyer-Olkin 0.65-0.78) and internal consistency (range 0.82-0.85) indicate each recovery domain is adequately assessed. The 7-item Relationship sub-scale has convergent validity 0.69, test-retest reliability 0.75, internal consistency 0.89, a one-factor solution (variance 70.5 %, KMO 0.84) and adequate sensitivity to change. A 5-item Brief INSPIRE was also evaluated.
INSPIRE and Brief INSPIRE demonstrate adequate psychometric properties, and can be recommended for research and clinical use.
We performed a cross-sectional study, in which a detailed assessment of psychosocial outcomes was made using validated questionnaires. Additional questions specific to donation were also asked, including questions regarding motivation, regret, and anonymity.
One hundred ninety responses were received from 296 participants studied (110 UKDs [74.3%] vs. 80 SKDs [54.1%], P<0.001). Unspecified kidney donors were older (54 years vs. 44 years; P<0.001), predominantly white (99.1% vs. 78.5%; P<0.001), and donated more recently (1.3 years vs. 2.6 years; P<0.001). There was no difference in psychiatric history or personality type, or current depression, anxiety, stress, self-esteem, or well-being between the groups (P>0.05). Unspecified kidney donors were more engaged in other altruistic behaviours (P<0.001). There was no difference in physical outcomes, although UKDs recovered quicker (P<0.001). Regret was low (3.7% UKDs vs. 7.5% SKDs; P=0.078).
This study has demonstrated that UKDs have comparable physical and psychosocial outcomes to SKDs. These favorable outcomes may be, in part, because of the rigorous evaluation process which currently includes a mental health assessment. We conclude that the program can continue to expand safely across the United Kingdom.
One hundred twelve patients either self-affirmed or completed a matched control task before reading about the risks associated with a lack of phosphate control. Serum phosphate was collected from baseline up to 12 months.
Self-affirmed patients had significantly reduced serum phosphate levels at 1 and 12 months. However, contrary to the predictions derived from self-affirmation theory, self-affirmed participants and controls did not differ in their evaluation of the health-risk information, behavioural intention or self-efficacy.
A low-cost, high-reach health intervention based on self-affirmation theory was shown to reduce serum phosphate over a 12 month period. Further work is required to identify mediators of the observed effects.
Age, sex, baseline DAS28, symptom duration, rheumatoid factor, fulfilment of the 1987 ACR criteria and socio-economic status (SES) were included as potential predictors of HAQ trajectory subgroup membership.
The literature search identified 49 studies showing that HAQ progression has mainly been based on average changes in the total study population. In the HAQ progression study, a LCGM with four HAQ trajectory subgroups was selected as providing the best fit in both cohorts. In both the cohorts, older age, female sex, longer symptom duration, fulfilment of the 1987 ACR criteria, higher DAS28 and lower SES were associated with increased likelihood of membership of subgroups with worse HAQ progression.
Four distinct HAQ trajectory subgroups were derived from the ERAS and NOAR cohorts. The fact that the subgroups identified were nearly identical supports their validity. Identifying distinct groups of patients who are at risk of poor functional outcome may help to target therapy to those who are most likely to benefit.
MEDLINE and Embase were searched for observational studies reporting mean and standard deviation scores for each domain of the SF-36 in adult RA patients. Studies were reviewed in accordance with PRISMA guidelines, and a random-effects meta-analysis was performed.
In total, 31 studies were eligible for inclusion in the meta-analysis, including 22,335 patients. Meta-analyses found that pooled mean HRQoL score for the SF-36 physical component summary was 34.1 (95% CI: 22.0-46.1) and mental component summary was 45.6 (95% CI: 30.3-60.8). Increased age was associated with reduced physical function and physical component summary (PCS) scores but improved mental health and mental component summary (MCS) scores. Female gender was associated with improved scores on role physical, bodily pain and PCS but reduced mental health and MCS scores. Longer disease duration was associated with improved MCS. Patients with RA have a substantially reduced HRQoL in comparison to both other physical illnesses and in comparison to normative datasets from UK and USA populations.
RA has a substantial impact on HRQoL. This supports recent NICE guidelines stipulating that RA patients should be regularly assessed for the impact their disease has on HRQoL and appropriate management provided.
The combined PAR associated with the risk factors was calculated using data from the Health Survey for England 2006 to estimate and adjust for the association between risk factors. The potential of risk factor reduction was assessed by examining the combined effect of relative reductions of 10% and 20% per decade for each of the seven risk factors on projections for Alzheimer's disease cases to 2050.
Worldwide, the highest estimated PAR was for low educational attainment (19·1%, 95% CI 12·3-25·6). The highest estimated PAR was for physical inactivity in the USA (21·0%, 95% CI 5·8-36·6), Europe (20·3%, 5·6-35·6), and the UK (21·8%, 6·1-37·7). Assuming independence, the combined worldwide PAR for the seven risk factors was 49·4% (95% CI 25·7-68·4), which equates to 16·8 million attributable cases (95% CI 8·7-23·2 million) of 33·9 million cases. However, after adjustment for the association between the risk factors, the estimate reduced to 28·2% (95% CI 14·2-41·5), which equates to 9·6 million attributable cases (95% CI 4·8-14·1 million) of 33·9 million cases. Combined PAR estimates were about 30% for the USA, Europe, and the UK. Assuming a causal relation and intervention at the correct age for prevention, relative reductions of 10% per decade in the prevalence of each of the seven risk factors could reduce the prevalence of Alzheimer's disease in 2050 by 8·3% worldwide.
After accounting for non-independence between risk factors, around a third of Alzheimer's diseases cases worldwide might be attributable to potentially modifiable risk factors. Alzheimer's disease incidence might be reduced through improved access to education and use of effective methods targeted at reducing the prevalence of vascular risk factors (eg, physical inactivity, smoking, midlife hypertension, midlife obesity, and diabetes) and depression.
National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care for Cambridgeshire and Peterborough.
Two groups of individuals sharing similar illness perception profiles were identified. The smaller group (43%), characterised by a negative representation of their illness, attributed more symptoms to their condition and reported stronger perceptions of the consequences, chronicity and cyclicality of their condition, and lower control compared to the positive representation group (57%). Cross-sectionally, membership of the negative representation group was associated with higher levels of pain and functional disability and, longitudinally, with increases in levels of pain, functional disability and distress. These data highlight the central role of illness perceptions in RA and suggest that individuals with RA can be categorised into groups with similar illness representations.
This study performed a secondary analysis of 140 women with problematic HFNS who were recruited to the MENOS2 trial: 48 were randomly assigned to group CBT, 47 were randomly assigned to self-help CBT, and 45 were randomly assigned to usual care. Self-report questionnaires were completed at baseline, 6 weeks postrandomization, and 26 weeks postrandomization. Potential moderators and mediators of treatment effects on the primary outcome-hot flush problem rating-were examined using linear mixed-effects models and path analysis, respectively.
CBT was effective at reducing HFNS problem rating regardless of age, body mass index, menopause status, or psychological factors at baseline. Fully reading the manual in the self-help CBT arm and completing most homework assignments in the group CBT arm were related to greater improvement in problem rating at 6 weeks. The effect of CBT on HFNS problem rating was mediated by changes in cognitions (beliefs about coping/control of hot flushes, beliefs about night sweats and sleep) but not by changes in mood.
These findings suggest that CBT is widely applicable for women having problematic HFNS, regardless of sociodemographic or health-related factors, and that CBT works mainly by changing the cognitive appraisal of HFNS.
Questionnaires were completed at baseline, 9 and 26 weeks post randomisation. Potential moderators and mediators, including sociodemographic, clinical and psychological factors, of the treatment effect on the primary outcome were examined.
Hot Flush Problem Rating.
CBT was effective at reducing problem rating at 9 weeks regardless of age, BMI, time since breast cancer diagnosis, menopausal status at time of diagnosis, or type of cancer treatment (radiotherapy or chemotherapy or endocrine treatment). The treatment effect was significantly greater in women not receiving chemotherapy, those with higher levels of psychological distress at baseline and for non-white women. Beliefs about control/coping with hot flushes were the main mediators of improvement in problem rating following CBT. Beliefs about hot flushes in a social context, depressed mood and sleep problems were also identified as mediators.
These findings suggest that CBT is widely applicable for breast cancer patients who are experiencing treatment related menopausal symptoms, and that CBT works mainly by changing beliefs and improving mood and sleep.
The use of disease-modifying antirheumatic drugs (DMARDs), corticosteroids, and biologic therapies reflected the contemporary conventional practices and guidelines of the time frames examined. Recruitment years were grouped into 6 periods, and interventions were classified into major, intermediate, and minor categories.
A total of 1,602 orthopedic surgical procedures were performed in 770 patients (29%) over a maximum of 25 years of followup. The 25-year cumulative incidence rate of major interventions was 21.7% (range 19.4-24.0%), and that of intermediate interventions was 21.5% (range 17.8-25.5%). There was a decline in the 10-year cumulative incidence of intermediate surgeries over time (P < 0.001), but not of major/minor surgery. This decline coincided with a gradual shift from sequential monotherapy to combination DMARD therapies and biologic agents in recent recruitment periods.
Orthopedic surgery is an important and common outcome in RA. Only the rates of hand/foot surgery showed a consistent decline from 1986 to 2011. Possible explanations include differences in the pathophysiologic processes affecting the joints, variations in the responses to therapy between large-joint and small-joint destructive processes, and changes in service provision and thresholds for surgery over time.
We undertook a scoping review including all types of research relating to the prevalence of comorbidities in people with dementia; current systems, structures and other issues relating to service organisation and delivery; patient and carer experiences; and the experiences and attitudes of service providers. We searched AMED, Cochrane Library, CINAHL, PubMed, NHS Evidence, Scopus, Google Scholar (searched 2012, Pubmed updated 2013), checked reference lists and performed citation searches on PubMed and Google Scholar (ongoing to February 2014).
We included 54 primary studies, eight reviews and three guidelines. Much of the available literature relates to the prevalence of comorbidities in people with dementia or issues around quality of care. Less is known about service organisation and delivery or the views and experiences of people with dementia and their family carers. There is some evidence that people with dementia did not have the same access to treatment and monitoring for conditions such as visual impairment and diabetes as those with similar comorbidities but without dementia.
The prevalence of comorbid conditions in people with dementia is high. Whilst current evidence suggests that people with dementia may have poorer access to services the reasons for this are not clear. There is a need for more research looking at the ways in which having dementia impacts on clinical care for other conditions and how the process of care and different services are adapting to the needs of people with dementia and comorbidity. People with dementia should be included in the debate about the management of comorbidities in older populations and there needs to be greater consideration given to including them in studies that focus on age-related healthcare issues.
Deaths were tracked by the National Health Service Central Register. Growth mixture modelling was used to identify distinct trajectories of HAQ score progression and survival analysis employed to compare all-cause mortality across the trajectory classes.
Four HAQ score progression classes were identified: moderate increasing (46%), low stable (6%), moderate stable (28%) and high stable (20%). Only the moderate-increasing class exhibited an accelerated decline in function over normal ageing. Compared with the moderate-increasing class, individuals with high-stable HAQ scores were more likely to be female, have more severe disease and other coexistent conditions. Low-stable class patients were more likely to be male and report less pain. The high-stable class had increased risk of mortality compared with the moderate-increasing class after adjusting for potential confounding factors, whereas low-stable and moderate-stable classes were at reduced mortality risk.
The effect of RA on function is set within the first few years and is affected by comorbidity. Identifying distinct groups of patients may help to target those at greater risk of poor functional outcome and mortality.
Latent class growth modelling identified distinct groups of depression symptom trajectories.
Three depression trajectories were identified: "low-reducing" (62 %), "moderate-increasing" (21.8 %) and "high-reducing" (16.2 %). Higher levels of depression were associated with a poorer understanding of the illness (coherence) and perceptions that kidney failure has severe consequences and a more cyclical timeline. Beliefs that treatment controlled kidney failure decreased over time in patients with increasing depression symptoms.
Distinct patterns of depression symptoms are associated with illness perceptions. The potential to identify common patterns of depression symptoms may help target treatments at those most likely to benefit.
Baseline prevalence was 31.6% and 8.6% for all comorbidities and extra-articular features, respectively, and 15-year cumulative incidence was 81% and 53%, respectively. Rates of hypertension [standardized incidence ratio (SIR) = 1.61; 95% CI 1.43, 1.79] and ischaemic heart disease (SIR = 1.60; 95% CI 1.35, 1.84) were raised compared with figures for the general population, as was stroke in females (SIR = 1.34; 95% CI 1.02, 1.77) and chronic obstructive pulmonary disorder in males (SIR = 1.63; 95% CI 1.17, 2.26). Comorbidity was associated with risk of both all-cause and cardiovascular mortality (hazard ratio = 1.09; 95% CI 1.02, 1.17) and increased rates of functional decline over 10 years (b = 0.011; 95% CI 0.004, 0.019). Comorbidity was not related to disease activity or structural damage.
Significant comorbidity was present at the outset of RA, increasing with follow-up, mainly in cardiovascular, non-cardiac vascular and respiratory systems. Specific conditions (e.g. hypertension) occurred more frequently than in the general population. Comorbidity was related to mortality and functional decline, and more intensive therapies may need consideration in these patients. As many co-existent conditions are amenable to preventative/therapeutic measures, comorbidity needs earlier detection and management in order to reduce its impact on outcome in RA.
The fit of each model was assessed separately in each sample and by meta CFA. Meta CFA was conducted using all samples and using subgroups consisting of community samples, cardiovascular disease samples and samples from studies administering the English language version of the HADS.
A bifactor model including all items loading onto a general distress factor and two orthogonal anxiety and depression group factors provided the best fit for the majority of samples. Meta CFA provided further support for the bifactor model with two group factors. This was the case using all samples, as well as all subgroup analyses. The general distress factor explained 73% of the covariance between items, with the (autonomic) anxiety and (anhedonic) depression factors explaining 11% and 16%, respectively.
A bifactor structure provides the most acceptable empirical explanation for the HADS correlation structure. Due to the presence of a strong general factor, the HADS does not provide good separation between symptoms of anxiety and depression. We recommend it is best used as a measure of general distress.
It is therefore important these projections are as accurate as possible.
In this paper we provide a commentary on studies projecting the future prevalence of dementia for the world or for individual continents. We identify some important limitations of the methods used in published projections and provide recommendations to improve the accuracy of future projections, and allow for the checking of the accuracy of the predictions.
Accurate projections of dementia incidence, at both the global and local level, are essential for healthcare planners.
Quality-of-life assessments (Short-Form 36, Hospital Anxiety and Depression Scale, and Satisfaction with Life Scale) were performed every 3 months for up to 3 years in patients with advanced, progressive CKD (late stage 4 and stage 5).
After 3 years, 80 and 44 of 170 patients had started or were planned for hemodialysis (HD) or peritoneal dialysis, respectively; 30 were undergoing CKM; and 16 remained undecided. Mean baseline estimated GFR ± SD was similar (14.0 ± 4.0 ml/min per 1.73 m(2)) in all groups but was slightly higher in undecided patients. CKM patients were older, more dependent, and more highly comorbid; had poorer physical health; and had higher anxiety levels than the dialysis patients. Mental health, depression, and life satisfaction scores were similar. Multilevel growth models demonstrated no serial change in quality-of-life measures except life satisfaction, which decreased significantly after dialysis initiation and remained stable in CKM. In Cox models controlling for comorbidity, Karnofsky performance scale score, age, physical health score, and propensity score, median survival from recruitment was 1317 days in HD patients (mean of 326 dialysis sessions) and 913 days in CKM patients.
Patients choosing CKM maintained quality of life. Adjusted median survival from recruitment was 13 months shorter for CKM patients than HD patients.
, Petrie, K. J., Horne, R., Cameron, L. D., & Buick, D. (2002). The revised Illness Perception Questionnaire (IPQ-R). Psychology & Health, 17 (1), 1-16.) Modifying the a-priori IPQ-R factor structure by removing two items with low factor loadings and specifying a path between personal control and item 23 had marginally better fit. A separate exploratory factor analysis of the causal items indicated three factors relating to Biological, Psychological and Behavioural causes. These findings provide evidence towards the validity and reliability of the IPQ-R as a suitable measure of illness perceptions in the context of ESRD.
Patients completed a questionnaire that assessed psychological distress and positive outlook (depression, anxiety and positive outlook scale), illness perceptions (IPQ-R) and functional disability (health assessment questionnaire). Information regarding prescribed medication and disease activity [disease activity score (DAS28)] was collected from medical notes. Psychological distress, but not positive outlook, was associated with functional disability and DAS28. After controlling for sex, age and DAS28, perceptions of greater symptomatology (identity) and lesser understanding of RA (coherence) were significantly associated with increased psychological distress. Perceptions of greater treatment control were associated with greater positive outlook, but only for those with low DAS28. Coherence was also associated with positive outlook. These findings indicate that illness perceptions may influence psychological distress and positive outlook in RA patients, and may therefore be a useful basis for future psychological interventions.
Standard clinical and radiological assessments were recorded at baseline and yearly. Point remission was defined by DAS of <1.6, and sustained remission if DAS was <1.6 at all 3-, 4- and 5-year follow-ups. Sustained remission was compared with baseline features, with mortality and with radiological and functional progression in 704 patients.
Point remission at 3, 4 and 5 years was 25, 26 and 22%, respectively. Eleven per cent (n = 78) had sustained remission. Male sex, short duration of symptoms and less tender joints at baseline were independent predictors of sustained remission. These patients had fewer DMARD therapies and less radiographic progression by 5 years. Mean HAQ decreased from 0.79 to 0.13 (P < 0.001) in sustained remission, compared with an increase from 0.92 to 1.1 (P < 0.001) in the non-remission group.
Sustained clinical remission by 5 years with conventional DMARDs was 11%, half as likely as point remission. Prognostic factors were similar to comparable studies and simple to measure. Patients in sustained clinical remission showed less structural damage and better functional outcomes.
This was a cross-sectional study of ESRD patients (n = 76). Non-adherence was measured in two ways: (1) the self-report Medication Adherence Questionnaire (MAQ) and (2) 3-month average level of serum phosphate. The Beliefs about Medicines questionnaire was used to assess general and specific beliefs towards phosphate medicines.
Eleven (14.5% of 76) patients reported being intentionally non-adherent to phosphate binders. Patients' beliefs that phosphate binders were less necessary were significantly associated with intentional self-reported non- adherence. Furthermore, patients with greater concerns about phosphate binders had higher serum phosphate levels.
Assessing patient beliefs about medicines is a reliable indicator of intentional non-adherence to treatment with phosphate binders. These findings may help in identifying ways in which adherence rates to phosphate binders can be improved.
A latent growth mixture modelling (GMM) approach was used to identify distinct psychological distress patterns.
Four distinct psychological distress trajectories were observed: low-stable (68%), high-stable (12%), high-decreasing (9%) and low-increasing (11%). Symptoms of pain, stiffness and functional impairment were significantly associated with levels of psychological distress at the time of diagnosis and after 3 years; serological markers of disease activity (ESR and CRP) were not.
Although the majority of individuals developing RA experience little or no impact of the effects of the disease on their psychological well-being, a significant proportion experience high levels of distress at some point which may be related to their subjective appraisal of their condition. Assessment and treatment of psychological distress should occur synchronously with somatic symptoms.
Competing models of the factor structure of the BDI were evaluated using confirmatory factor analysis.
The best fitting model consisted of general depression factor that accounted for 81% of the common variance between all items along with orthogonal cognitive and somatic factors (G-S-C model, CFI=.983, TLI=.979, RMSEA=.037), which explained 8% and 9% of the common variance, respectively. Age, diabetes, and ethnicity were significantly related to the cognitive factor, whereas albumin, dialysis adequacy, and ethnicity were related to the somatic factor. No demographic or clinical variable was associated with the general factor.
The general-factor model provides the best fitting and conceptually most acceptable interpretation of the BDI. Furthermore, the cognitive and somatic factors appear to be related to specific demographic and clinical factors.
We examine its incidence, outcome and prognostic indicators.
Extra-articular features and comorbidity have been recorded yearly in a well-established inception cohort of RA with a 20-year follow-up. Standard clinical, laboratory and radiological measures of RA were recorded at baseline and yearly. Details of deaths were provided by a national central register.
Out of 1460 patients, 52 developed RA-ILD, half either at baseline or within 3 years of onset. The annualized incidence was 4.1/1000 (95% CI 3.0, 5.4) and the 15-year cumulative incidence 62.9/1000 (95% CI 43.0, 91.7). Incidence of RA-ILD was associated with older age, raised baseline ESR and HAQ. Evidence to implicate any drug effect (e.g. MTX) was lacking. Of these patients, 39 died, attributed to RA-ILD in 28. Median survival following diagnosis of RA-ILD was 3 years.
RA-ILD is an important and early feature of RA. It is related to disease activity and has a poor prognosis. Further studies are required to determine whether screening for pulmonary disease would identify these patients at an earlier stage.