Health status measurement in patients with severe asthma

  • Author Footnotes
    1 These authors contributed equally to this work.
    Jeannette B. Peters
    Correspondence
    Corresponding author. Department of Medical Psychology and Department of Pulmonary Diseases, Radboud University Nijmegen Medical Centre, Postbus 66, 6560 AB Groesbeek, The Netherlands. Tel.: +31 24 6859557; fax: +31 24 6859531.
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Department of Medical Psychology, Radboud University Nijmegen Medical Centre, Nijmegen, Postbus 66, 6560 AB Groesbeek, The Netherlands

    Department of Pulmonary Diseases, Radboud University Nijmegen Medical Centre, Nijmegen, Postbus 66, 6560 AB Groesbeek, The Netherlands
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  • Author Footnotes
    1 These authors contributed equally to this work.
    Lucia H. Rijssenbeek-Nouwens
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Dutch Asthma Centre Davos, Herman Burchartstrasse 1, 7260 Davos, Switzerland
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  • Aad O. Bron
    Affiliations
    Dutch Asthma Centre Davos, Herman Burchartstrasse 1, 7260 Davos, Switzerland
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  • Karin B. Fieten
    Affiliations
    Dutch Asthma Centre Davos, Herman Burchartstrasse 1, 7260 Davos, Switzerland
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  • Els J.M. Weersink
    Affiliations
    Department of Respiratory Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
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  • Elisabeth H. Bel
    Affiliations
    Department of Respiratory Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
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  • Jan H. Vercoulen
    Affiliations
    Department of Medical Psychology, Radboud University Nijmegen Medical Centre, Nijmegen, Postbus 66, 6560 AB Groesbeek, The Netherlands

    Department of Pulmonary Diseases, Radboud University Nijmegen Medical Centre, Nijmegen, Postbus 66, 6560 AB Groesbeek, The Netherlands
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  • Author Footnotes
    1 These authors contributed equally to this work.
Open ArchivePublished:December 04, 2013DOI:https://doi.org/10.1016/j.rmed.2013.11.012

      Summary

      Background

      Patients with severe asthma experience problems in different areas of their health status. Identification of these areas will provide insight in the patients needs and perhaps what determines the burden of disease. The Nijmegen Clinical Screening Instrument (NCSI) was recently developed for use in clinical practice in patients with COPD and provides a detailed picture of the patients' physiological functioning, symptoms, functional impairment, and Quality of Life. Main purpose of this study is to evaluate the use of the NCSI as compared to the Asthma Control Questionnaire (ACQ) and Asthma Quality of Life Questionnaire (AQLQ) in patients with severe asthma.

      Methods

      The NCSI, AQLQ, and ACQ were measured in 167 patients with severe asthma. Pearson correlations were calculated between NCSI sub-domains and the AQLQ domains and the ACQ.

      Results

      The NCSI measures more aspects of health status as compared to the ACQ and AQLQ in patients with severe asthma. Beside symptoms, subjective impairment, and emotions the NCSI also measures general Quality of Life, health related Quality of Life, satisfaction with relations, fatigue, and behavioural impairment. On all NCSI sub-domains proportions of patients with normal, mild, and severe problems were found. Heterogeneity was found on the number and on the combination of sub-domains on which patients reported severe problems.

      Conclusions

      The NCSI provides a more detailed picture of the individual patient with severe asthma than the ACQ and AQLQ. The use of the NCSI might allow quick identification of the problem areas and possible factors that impair health status.

      Keywords

      Introduction

      Patients with severe asthma suffer from serious problems in health status, such as symptoms during day- and nighttime [
      • Juniper E.F.
      • Guyatt G.H.
      • Epstein R.S.
      • Ferrie P.J.
      • Jaeschke R.
      • Hiller T.K.
      Evaluation of impairment of health related quality of life in asthma: development of a questionnaire for use in clinical trials.
      ], impairments in daily life activities [
      • Haselkorn T.
      • Chen H.
      • Miller D.P.
      • Fish J.E.
      • Peters S.P.
      • Weiss S.T.
      • et al.
      Asthma control and activity limitations: insights from the Real-world Evaluation of Asthma Control and Treatment (REACT) study.
      ], and lower Quality of Life (QoL) [
      • Centanni S.
      • Di Marco F.
      • Castagna F.
      • Boveri B.
      • Casanova F.
      • Piazzini A.
      Psychological issues in the treatment of asthmatic patients.
      ,
      • Katz P.P.
      • Morris A.
      • Julian L.
      • Omachi T.
      • Yelin E.H.
      • Eisner M.D.
      • et al.
      Onset of depressive symptoms among adults with asthma: results from a longitudinal observational cohort.
      ,
      • Lavoie K.L.
      • Bacon S.L.
      • Barone S.
      • Cartier A.
      • Ditto B.
      • Labrecque M.
      What is worse for asthma control and quality of life: depressive disorders, anxiety disorders, or both?.
      ,
      • Lavoie K.L.
      • Bouthillier D.
      • Bacon S.L.
      • Lemiere C.
      • Martin J.
      • Hamid Q.
      • et al.
      Psychologic distress and maladaptive coping styles in patients with severe vs moderate asthma.
      ]. For adequate assessment and management of patients with severe asthma a detailed evaluation of patients' needs would be helpful to identify the factors that influence their health status. An instrument that provides a detailed picture of the different aspects of the patient's health status would be very useful. This information would guide treatment, help to open up the communication with the patient, and to improve the patient's self-management.
      Many disease specific and generic questionnaires exist that measure aspects of health status. In asthma the Asthma control Questionnaire (ACQ) and Asthma Quality of Life Questionnaire (AQLQ) and to a lesser extend the, St George Respiratory Questionnaire (SGRQ) and Quality of Life for Respiratory Illness Questionnaire (QoL-RiQ) are used for this purpose [
      • Juniper E.F.
      • Bousquet J.
      • Abetz L.
      • Bateman E.D.
      • Committee G.
      Identifying ‘well-controlled’ and ‘not well-controlled’ asthma using the Asthma Control Questionnaire.
      ,
      • Juniper E.F.
      • Buist A.S.
      • Cox F.M.
      • Ferrie P.J.
      • King D.R.
      Validation of a standardized version of the Asthma Quality of Life Questionnaire.
      ,
      • Jones P.W.
      • Quirk F.H.
      • Baveystock C.M.
      The St-George Respiratory Questionnaire.
      ,
      • Maille A.R.
      • Koning C.J.
      • Zwinderman A.H.
      • Willems L.N.
      • Dijkman J.H.
      • Kaptein A.A.
      The development of the ‘Quality-of-life for Respiratory Illness Questionnaire (QOL-RIQ)’: a disease-specific quality-of-life questionnaire for patients with mild to moderate chronic non-specific lung disease.
      ]. These instruments, especially the AQLQ and ACQ, are widely used in research, have proven to be valid, reliable, and are able to measure change, to describe groups and effects of interventions. However, on the level of the individual patient and in clinical care these instruments seem less appropriate. The ACQ only indicates whether the asthma is controlled or uncontrolled in a patient and provides no information on health status. The AQLQ measures only four domains, and lacks normative data, which means that the clinical relevance of particular scores on the level of the individual patient is unclear.
      The Nijmegen Clinical Screening Instrument (NCSI) was specifically developed for use in clinical care of patients with COPD, to detect the problems in health status on individual patient base. [
      • Peters J.B.
      • Daudey L.
      • Heijdra Y.F.
      • Molema J.
      • Dekhuijzen P.N.
      • Vercoulen J.H.
      Development of a battery of instruments for detailed measurement of health status in patients with COPD in routine care: the Nijmegen Clinical Screening Instrument.
      ] The NCSI measures eleven sub-domains of health status covering aspects of physiological functioning, symptoms, functional impairment and Quality of Life with a battery of subscales from disease specific and generic questionnaires, as well as the results of lung function test. For each sub-domain of the NCSI normative data indicating normal functioning, mild problems and severe problems were collected. Immediately after the patient has completed the questionnaire part on the computer, are the results presented on the graphical PatientProfileChart (Fig. 1) [
      • Peters J.B.
      • Daudey L.
      • Heijdra Y.F.
      • Molema J.
      • Dekhuijzen P.N.
      • Vercoulen J.H.
      Development of a battery of instruments for detailed measurement of health status in patients with COPD in routine care: the Nijmegen Clinical Screening Instrument.
      ].
      Figure thumbnail gr1
      Figure 1The PatientProfileChart a graphical representation of the patient's scores on the diverse aspects of health status as measured by the NCSI. Note: in this figure we plotted the mean score of the study group (blue dots) on that particular aspect instead of the individual score which is normally plotted in the graphs. The green area represents normal functioning, yellow area mild problems, and red area severe problems. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
      Although developed and validated in patients with COPD [
      • Peters J.B.
      • Daudey L.
      • Heijdra Y.F.
      • Molema J.
      • Dekhuijzen P.N.
      • Vercoulen J.H.
      Development of a battery of instruments for detailed measurement of health status in patients with COPD in routine care: the Nijmegen Clinical Screening Instrument.
      ], have previous studies shown that all NCSI sub-domains are relevant in other diseases as well, including Q-fever [
      • Limonard G.J.
      • Peters J.B.
      • Nabuurs-Franssen M.H.
      • Weers-Pothoff G.
      • Besselink R.
      • Groot C.A.
      • et al.
      Detailed analysis of health status of Q fever patients 1 year after the first Dutch outbreak: a case-control study.
      ,
      • Morroy G.
      • Peters J.B.
      • van Nieuwenhof M.
      • Bor H.H.
      • Hautvast J.L.
      • van der Hoek W.
      • et al.
      The health status of Q-fever patients after long-term follow-up.
      ], and cardiac diseases (submitted). We hypothesized that the NCSI can be used also in patients with asthma. Asthma and COPD have overlapping clinical characteristics and both patient groups report similar problems in health status. Moreover, patients with severe asthma are known to experience severe symptoms, functional impairment, and lower QoL [
      • Juniper E.F.
      • Guyatt G.H.
      • Epstein R.S.
      • Ferrie P.J.
      • Jaeschke R.
      • Hiller T.K.
      Evaluation of impairment of health related quality of life in asthma: development of a questionnaire for use in clinical trials.
      ,
      • Haselkorn T.
      • Chen H.
      • Miller D.P.
      • Fish J.E.
      • Peters S.P.
      • Weiss S.T.
      • et al.
      Asthma control and activity limitations: insights from the Real-world Evaluation of Asthma Control and Treatment (REACT) study.
      ,
      • Centanni S.
      • Di Marco F.
      • Castagna F.
      • Boveri B.
      • Casanova F.
      • Piazzini A.
      Psychological issues in the treatment of asthmatic patients.
      ,
      • Katz P.P.
      • Morris A.
      • Julian L.
      • Omachi T.
      • Yelin E.H.
      • Eisner M.D.
      • et al.
      Onset of depressive symptoms among adults with asthma: results from a longitudinal observational cohort.
      ,
      • Lavoie K.L.
      • Bacon S.L.
      • Barone S.
      • Cartier A.
      • Ditto B.
      • Labrecque M.
      What is worse for asthma control and quality of life: depressive disorders, anxiety disorders, or both?.
      ,
      • Lavoie K.L.
      • Bouthillier D.
      • Bacon S.L.
      • Lemiere C.
      • Martin J.
      • Hamid Q.
      • et al.
      Psychologic distress and maladaptive coping styles in patients with severe vs moderate asthma.
      ]. Therefore, a group of patients with severe asthma would be most suitable to examine whether the NCSI can identify problems in health status in patients with severe asthma.
      The main purpose of this study is to evaluate the NCSI in measuring the unmet needs in patients with severe asthma. The primary aim is to evaluate the internal consistency of the NCSI, and to investigate the relationships between the sub-domains of the NCSI, the ACQ total, and the AQLQ domains in patients with severe asthma. The secondary aim is to evaluate to what extent the NCSI measures other sub-domains of health status as compared to the disease specific AQLQ and ACQ, and whether these sub-domains are relevant in patients with severe asthma.

      Materials and methods

       Study design

      This cross-sectional study was conducted in patients with severe asthma who were referred to the Dutch Asthma Centre in Davos for high altitude treatment. On admission, all patients were assessed according to a systematic protocol. The study was approved by the Medical Ethical Committee of the Amsterdam Medical Centre and the approval was adopted by the Asthma Centre Davos. Written informed consent was obtained from all patients participating in the study. All data was collected in usual care, shortly after admission, and anonymized before analysis.

       Study population

      Adult patient (18–75 years) with a diagnosis of severe asthma who were referred to the Dutch Asthma Centre Davos, Switzerland, between January 2008 and January 2010 were asked to participate in the study. Severe asthma was defined according to the international criteria [
      • Bel E.H.
      • Sousa A.
      • Fleming L.
      • Bush A.
      • Chung K.F.
      • Versnel J.
      • et al.
      Diagnosis and definition of severe refractory asthma: an international consensus statement from the Innovative Medicine Initiative (IMI).
      ]. Dutch lung physicians send patients with severe asthma to the high altitude clinic in Davos, when optimal treatment, according to the GINA guidelines at sea level is not enough to reach control of asthma. [
      • National Institutes of Health. National Heart, Lung, and Blood Institute. Global Initiative for Asthma
      Global strategy for asthma management and prevention.
      ] All patients were prescribed high doses of inhaled corticosteroids (≥1000 μg·day of fluticasone or equivalent) or oral corticosteroids, combined with long-acting bronchodilators for at least 1 year, in accordance to the GINA Guidelines stages 4–6 [
      • National Institutes of Health. National Heart, Lung, and Blood Institute. Global Initiative for Asthma
      Global strategy for asthma management and prevention.
      ]. Most patients also used additional asthma medications (e.g. antihistamines, montelukast, theaphylline etc). Patients with a smoking history >15 years, had to show reversibility in FEV1 to short-acting beta agonist >12% predicted in order to exclude patients with smoking related COPD. All patients were symptomatic and had experienced at least one severe exacerbation during the past year requiring a course of oral corticosteroids. Before referral to the high altitude clinic, inhalation technique and adherence with treatment was checked by the referring pulmonologist.

       Questionnaires

      AQLQ. The Asthma Quality of Life Questionnaire standardized version (AQLQ-S) [
      • Juniper E.F.
      • Guyatt G.H.
      • Epstein R.S.
      • Ferrie P.J.
      • Jaeschke R.
      • Hiller T.K.
      Evaluation of impairment of health related quality of life in asthma: development of a questionnaire for use in clinical trials.
      ,
      • Juniper E.F.
      • Buist A.S.
      • Cox F.M.
      • Ferrie P.J.
      • King D.R.
      Validation of a standardized version of the Asthma Quality of Life Questionnaire.
      ] measures four domains: symptoms, activity limitation, emotional function, and environmental stimuli. Score range from 1 to 7, lower scores indicate more problems.
      ACQ. The Asthma Control Questionnaire (ACQ) [
      • Juniper E.F.
      • Bousquet J.
      • Abetz L.
      • Bateman E.D.
      • Committee G.
      Identifying ‘well-controlled’ and ‘not well-controlled’ asthma using the Asthma Control Questionnaire.
      ,
      • Juniper E.F.
      • O'Byrne P.M.
      • Guyatt G.H.
      • Ferrie P.J.
      • King D.R.
      Development and validation of a questionnaire to measure asthma control.
      ] consists of six items which are scored from 0 (totally controlled) to 6 (severely uncontrolled) covering day and nighttime symptoms, activity limitations and rescue bronchodilator use. The cut-off point for well controlled asthma is lower than 1.5 [
      • Juniper E.F.
      • Bousquet J.
      • Abetz L.
      • Bateman E.D.
      • Committee G.
      Identifying ‘well-controlled’ and ‘not well-controlled’ asthma using the Asthma Control Questionnaire.
      ].
      NCSI. The Nijmegen Clinical Screening Instrument (NCSI) [
      • Peters J.B.
      • Daudey L.
      • Heijdra Y.F.
      • Molema J.
      • Dekhuijzen P.N.
      • Vercoulen J.H.
      Development of a battery of instruments for detailed measurement of health status in patients with COPD in routine care: the Nijmegen Clinical Screening Instrument.
      ] is a battery of existing tests and disease specific and generic instruments that provide a detailed assessment of health status. The NCSI covers four main domains: physiological functioning, symptoms, functional impairment, and Quality of Life. These main domains are subdivided into eleven sub-domains that measure: airflow, body composition, static lung volumes (excluded in the present study), subjective symptoms, dyspnoea emotions, fatigue, behavioural impairment, subjective impairment, general QoL, health related QoL, and satisfaction relations. See Table 1 [
      • Maille A.R.
      • Koning C.J.
      • Zwinderman A.H.
      • Willems L.N.
      • Dijkman J.H.
      • Kaptein A.A.
      The development of the ‘Quality-of-life for Respiratory Illness Questionnaire (QOL-RIQ)’: a disease-specific quality-of-life questionnaire for patients with mild to moderate chronic non-specific lung disease.
      ,
      • Beck A.T.
      • Guth D.
      • Steer R.A.
      • Ball R.
      Screening for major depression disorders in medical inpatients with the Beck Depression Inventory for Primary Care.
      ,
      • Bergner M.
      Development, testing, and use of sickness impact profile.
      ,
      • Diener E.
      • Emmons R.A.
      • Larsen R.J.
      • Griffin S.
      The satisfaction with life scale.
      ,
      • Vercoulen J.H.
      • Daudey L.
      • Molema J.
      • Vos P.J.
      • Peters J.B.
      • Top M.
      • et al.
      An integral assessment framework of health status in chronic obstructive pulmonary disease (COPD).
      ,
      • Vercoulen J.H.
      • Swanink C.M.A.
      • Galama J.M.D.
      • Fennis J.F.M.
      • van der Meer J.W.M.
      • Bleijenberg G.
      Dimensional assessment in chronic fatigue syndrome.
      ,
      • Bergner M.
      • Bobbitt R.A.
      • Carter W.B.
      • Gilson B.S.
      The sickness impact profile: development and final revision of a health status measure.
      ] for the definitions of the sub-domains and the included tests and instruments by which these sub-domains are measured. Completion of the questionnaire part of the NCSI is computerized [
      • Bergner M.
      • Bobbitt R.A.
      • Carter W.B.
      • Gilson B.S.
      The sickness impact profile: development and final revision of a health status measure.
      ] and scoring is automated. Normative data for each subscale were collected in healthy subjects and different samples of patients with COPD to identify cut-offs scores indicating normal functioning, mild problems or severe problems [
      • Peters J.B.
      • Daudey L.
      • Heijdra Y.F.
      • Molema J.
      • Dekhuijzen P.N.
      • Vercoulen J.H.
      Development of a battery of instruments for detailed measurement of health status in patients with COPD in routine care: the Nijmegen Clinical Screening Instrument.
      ]. For each patient a personal profile can be made visible on the PatientProfileChart, see Fig. 1. For all sub-domains: the higher the score the more problematic.
      Table 1Domains, sub-domains, definitions, instruments and number of included items from the instrument of the questionnaire part of the Nijmegen Clinical Screening Instrument (NCSI).
      DomainSub-domainDefinitionInstruments/measurementNo of items
      Physiological functioningAirflowPost bronchodilator FEV1% predicted
      Body compositionBody Mass Index
      SymptomsSubjective symptomsThe patient's overall burden of pulmonary symptomsPARS-D Global Dyspnea Activity
      • Diener E.
      • Emmons R.A.
      • Larsen R.J.
      • Griffin S.
      The satisfaction with life scale.
      2
      PARS-D Global Dyspnea Burden
      • Diener E.
      • Emmons R.A.
      • Larsen R.J.
      • Griffin S.
      The satisfaction with life scale.
      Dyspnoea emotionsThe level of frustration and anxiety a person experiences when dyspnoeicDEQ Frustration
      • Diener E.
      • Emmons R.A.
      • Larsen R.J.
      • Griffin S.
      The satisfaction with life scale.
      6
      DEQ Anxiety
      • Diener E.
      • Emmons R.A.
      • Larsen R.J.
      • Griffin S.
      The satisfaction with life scale.
      FatigueThe level of experienced fatigueCIS Subjective fatigue
      • Vercoulen J.H.
      • Daudey L.
      • Molema J.
      • Vos P.J.
      • Peters J.B.
      • Top M.
      • et al.
      An integral assessment framework of health status in chronic obstructive pulmonary disease (COPD).
      8
      Functional impairmentBehavioural impairmentThe extent to which a person cannot perform specific and concrete activities as a result of having the diseaseSIP Home Management
      • Vercoulen J.H.
      • Swanink C.M.A.
      • Galama J.M.D.
      • Fennis J.F.M.
      • van der Meer J.W.M.
      • Bleijenberg G.
      Dimensional assessment in chronic fatigue syndrome.
      22
      SIP Ambulation
      • Vercoulen J.H.
      • Swanink C.M.A.
      • Galama J.M.D.
      • Fennis J.F.M.
      • van der Meer J.W.M.
      • Bleijenberg G.
      Dimensional assessment in chronic fatigue syndrome.
      Subjective impairmentThe experienced degree of impairment in generalQoLRiQ General Activities
      • Maille A.R.
      • Koning C.J.
      • Zwinderman A.H.
      • Willems L.N.
      • Dijkman J.H.
      • Kaptein A.A.
      The development of the ‘Quality-of-life for Respiratory Illness Questionnaire (QOL-RIQ)’: a disease-specific quality-of-life questionnaire for patients with mild to moderate chronic non-specific lung disease.
      4
      Quality of LifeGeneral Quality of LifeMood and the satisfaction of a person with his/her life as a wholeBDI Primary Care
      • Juniper E.F.
      • O'Byrne P.M.
      • Guyatt G.H.
      • Ferrie P.J.
      • King D.R.
      Development and validation of a questionnaire to measure asthma control.
      12
      Satisfaction With Life Scale
      • Bergner M.
      Development, testing, and use of sickness impact profile.
      Health-related Quality of LifeSatisfaction related to physical functioning and the futureSatisfaction physiological functioning
      • Diener E.
      • Emmons R.A.
      • Larsen R.J.
      • Griffin S.
      The satisfaction with life scale.
      2
      Satisfaction future
      • Diener E.
      • Emmons R.A.
      • Larsen R.J.
      • Griffin S.
      The satisfaction with life scale.
      Satisfaction relationsSatisfaction with the (absent) relationships with spouse and othersSatisfaction spouse
      • Diener E.
      • Emmons R.A.
      • Larsen R.J.
      • Griffin S.
      The satisfaction with life scale.
      2
      Satisfaction social
      • Diener E.
      • Emmons R.A.
      • Larsen R.J.
      • Griffin S.
      The satisfaction with life scale.
      PARS-D: Physical Activity Rating Scale-Dyspnea; DEQ: Dyspnea Emotions Questionnaire; CIS: Checklist Individual Strength; SIP: Sickness Impact Profile; QoLRiQ: Quality of Life for Respiratory Illness Questionnaire; BDI, Beck Depression Inventory.

       Measures

      Lung function parameters. Forced expiratory volume in 1 s (FEV1) was assessed after maintenance medication and inhalation of 400 μg salbutamol. Exhaled nitric oxide measurements were performed by standardized method [
      • American Thoracic S
      • European Respiratory S
      ATS/ERS recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide, 2005.
      ] using the NIOX.
      Sensitization to specific IgE was assessed with a panel of common aero-allergens (house dust mite, mixed grass and birch pollen, cat and dog dander and Aspergillus) by UniCap and expressed in kU/L. Patients were classified as allergic sensitized if IgE to one or more allergens was >0.35 kU/L.

       Statistics

      Data are presented as mean ± standard deviation (SD), unless stated otherwise. Cronbach's Alpha reliability coefficients were calculated to study the internal consistency reliability of the items of each sub-domain/subscale of the NCSI, ACQ and AQLQ, an α > 0.70 is considered reliable. Pearson correlation coefficients were calculated to study the relationships between the sub-domains of the NCSI, the ACQ total, and the subscales of the AQLQ. Conceptual similarity was defined by a correlation of 0.70 or higher. To avoid Type I error due to multiple testing P was set at 0.01. All statistics were performed by using SPSS 16.0 (SPSS Inc, Chicago, IL.).

      Results

       Subject characteristics

      One hundred and eighty patients were admitted to the high altitude clinic between January 2008 and January 2010, of which 167 agreed to participate in the study. Thirteen patients were not able to fill the questionnaires adequately because of illiteracy or did not agree to participate for personal reasons. The baseline characteristics of the 167 patients with severe asthma included in this study are presented in Table 2. Uncontrolled asthma was found in 91% (ACQ >1.5) of the patients in this study.
      Table 2Patient characteristics (N = 167). Data are presented as N (%), mean ± SD or median (range), unless otherwise stated.
      Age (yrs)44.5 ± 15
      Sex (male) N (%)58 (35%)
      Asthma duration (yrs)30 (1–66)
      Sensitized to allergens112 (67%)
      BMI28.1 (range 16.8–54.5)
      Ex-smokers57 (34%)
      FEV1% pred.87.7 ± 24.5
      FeNO ppb20.7 (4–233)
      ACQ score3.2 ± 1.1
      ICS μg/day0–8000
      Daily OCS N (%)82 (49%)
      BMI: body mass index; FEV1: forced expiratory volume in 1 s; % pred: % predicted; FeNO: exhaled nitric oxide fraction; ACQ: Asthma Control Questionnaire score, 0-6, where 0 = well controlled; ICS: inhalation corticosteroids; OCS: oral corticosteroids.

       NCSI-scores in severe asthma patients

      Overall, high percentages of severe problems were found in the sub-domains of symptoms, functional impairment, and QoL Fig. 2. The most prevalent sub-domains with severe impairment were subjective symptoms (82.0%), fatigue (90.4%), subjective impairment (86.8%), and general QoL (81.4%). Furthermore, 31.7% of the patients had clinically relevant depressive symptoms (subscale within sub-domain general QoL, not shown).
      Figure thumbnail gr2
      Figure 2Percentages of patients with asthma with normal functioning, mild problems and severe problems for each sub-domain of the NCSI.
      Diversity between patients was found in the number of sub-domains with severe problems (Fig. 3). Nineteen percent of patients were severely impaired in all eight sub-domains of the NCSI, and 80% of patients had five or more severely impaired sub-domains.
      Figure thumbnail gr3
      Figure 3Distribution of percentages of patients with severe asthma with severe problems on n number of sub-domains of the NCSI.

       Intercorrelations of the questionnaires

      With respect to the AQLQ, the domain activity reached conceptual similarity with the domain symptoms and environmental stimuli, although the latter two domains were only moderately related (Table 3).
      Table 3Correlations between the subscales of the Asthma Control Questionnaire (ACQ) and domains of the Asthma Quality of Life Questionnaire (AQLQ).
      ACQ totalAQLQ

      Symptoms
      AQLQ

      Activity limitation
      AQLQ

      Emotional function
      AQLQ

      Environmental stimuli
      AQLQ total
      ACQTotal1.00
      AQLQSymptoms0.831.00
      AQLQActivity limitations−0.670.851.00
      AQLQEmotional stimuli−0.350.540.391.00
      AQLQEnvironmental stimuli−0.350.480.690.341.00
      AQLQTotal−0.740.900.910.640.731.00
      Note. N = 167. Correlations >0.70 in bold.
      Correlations between most of the NCSI sub-domains were moderate to absent, as shown in Table 4. Only the sub-domains subjective symptoms and subjective impairment reached the criterion for conceptual similarity (r > 0.70), indicating that these two sub-domains measure highly related concepts.
      Table 4Correlations between the sub-domains of the Nijmegen Clinical Screening Instrument (NCSI).
      NCSI main domainSub-domainSymptomsFunctional impairmentQuality of Life
      Subjective symptomsDyspnoea emotionsFatigueSubjective impairmentBehavioural impairment#General QoLHealth related QoLSatisfaction relations
      Physiological functioningFEV1% of predicted−0.23−0.13ns0.04ns−0.19ns−0.19ns−0.05ns−0.07ns−0.14ns
      FeNO0.09ns0.18ns−0.15ns0.06ns−0.09ns0.14ns0.04ns−0.01ns
      BMI0.230.05ns0.01ns0.230.23ns0.03ns0.17ns0.01ns
      SymptomsSubjective symptoms1.00
      Dyspnoea emotions0.351.00
      Fatigue0.370.09ns1.00
      Functional impairmentSubjective impairment0.710.250.461.00
      Behavioural impairment0.34ns0.18ns0.32ns0.341.00
      Quality of LifeGeneral QoL0.240.670.20ns0.230.34ns1.00
      Health related QoL0.470.430.410.540.430.671.00
      Satisfaction relations0.17ns0.290.09ns0.20ns0.26ns0.520.451.00
      Note. N = 167 except for behavioural impairment due to a technical error (N = 53).

       Reliability of the questionnaires

      For all sub-domains the internal consistency was good, irrespective of the questionnaire used, except for the NCSI sub-domains of QoL see Table 5. However, the Cronbach's alpha of the two separate subscales that together measure general QoL was good (Satisfaction With Life Scale (SWLS) 0.88 and Beck's Depression Inventory (BDI) 0.83), respectively.
      Table 5Cronbach's reliability coefficient (α), score range, mean (SD) and 95% confidence interval of the three questionnaires, the Asthma Control Questionnaire (ACQ), the Asthma Quality of Life Questionnaire (AQLQ) and the Nijmegen Clinical Screening Instrument (NCSI) in patients with severe asthma (N = 167).
      Cronbach's alphaScore rangeMean ± SD95% CI
      ACQ total0.870–63.2 ± 1.12.9–3.3
      AQLQ
       Symptoms0.881–7
      Lower scores indicate more problems.
      3.9 ± 1.13.7–4.1
       Activity limitation0.881–7
      Lower scores indicate more problems.
      3.5 ± 1.23.3–3.6
       Emotional function0.841–7
      Lower scores indicate more problems.
      4.9 ± 1.34.7–5.1
       Environmental stimuli0.771–7
      Lower scores indicate more problems.
      4.2 ± 1.54.0–4.5
       Total1–7
      Lower scores indicate more problems.
      4.0 ± 1.03.8–4.1
      NCSI-symptoms
       Subjective symptoms0.892–2014.1 ± 4.213.5–14.8
       Dyspnoea emotions0.836–2412.0 ± 4.011.4–12.6
       Fatigue0.828–5647.1 ± 8.745.8–48.5
      NCSI-functional impairment
       Behavioural impairment0.790–99.226.2 ± 20.520.5–31.8
       Subjective impairment0.894–2817.7 ± 5.416.9–18.5
      NCSI-Quality of Life
       General QoL0.541–101.628.0 ± 17.825.3–30.7
       Health related QoL0.472–106.1 ± 1.75.8–6.3
       Satisfaction relations0.622–104.1 ± 2.03.8–4.4
      Note. Pearson correlations between the sub-domains of the NCSI, the ACQ, and the AQLQ for patients with asthma at start of rehabilitation. N = 167 except for behavioural impairment due to technical error (N = 53).
      a Lower scores indicate more problems.

       Conceptual similarity between the questionnaires

      The ACQ-total score reached conceptual similarity with AQLQ-symptoms and nearly with AQLQ-activity limitations (Table 6). The ACQ-total showed conceptual similarity only with NCSI subjective impairment, and nearly with NCSI subjective symptoms.
      Table 6Correlations between the sub-domains of the Nijmegen Clinical screening Instrument (NCSI), the Asthma Control Questionnaire (ACQ), and the Asthma Quality of Life Questionnaire (AQLQ) to examine conceptual similarity.
      ACQ totalAQLQ

      Symptoms
      AQLQ

      Activity limitation
      AQLQ

      Emotional function
      AQLQ

      Environmental stimuli
      AQLQ total
      Physiological functioning
       FEV1% predicted−0.260.16ns0.09ns0.20ns0.01ns0.14ns
       FeNO0.12ns−0.07ns0.05ns−0.12ns0.19ns0.01ns
       BMI0.18ns−0.12ns−0.16ns−0.07ns−0.02ns−0.13ns
      NCSI symptoms
       Subjective symptoms0.66−0.67−0.58−0.40−0.29−0.64
       Dyspnoea emotions0.21−0.30−0.16ns−0.69−0.16ns−0.36
       Fatigue0.44−0.47−0.43−0.16ns−0.19ns−0.43
      NCSI functional impairment
       Behavioural impairment0.49−0.53−0.59−0.41−0.39−0.60
       Subjective impairment0.77−0.70−0.65−0.37−0.30−0.68
      NCSI Quality of Life
       General QoL0.18ns−0.29−0.21−0.54−0.23−0.36
       Health related QoL0.40−0.46−0.42−0.50−0.24−0.50
       Satisfaction relations0.15ns−0.18ns−0.25−0.31−0.23−0.27
      Note. Pearson correlations between the sub-domains of the Nijmegen Clinical screening Instrument (NCSI), the Asthma Control Questionnaire (ACQ), and the Asthma Quality of Life Questionnaire (AQLQ) for patients with difficult to control asthma at start of rehabilitation. N = 167 except for behavioural impairment due to technical error (N = 53). Correlations >0.70 in bold.
      ns = not significant P > 0.01. Correlations in ‘bold-italic’ reach conceptual similarity.
      The AQLQ-symptoms showed conceptual similarity with NCSI subjective impairment, and nearly with NCSI subjective symptoms. AQLQ-activity limitations nearly reached conceptual similarity with NCSI subjective impairment. AQLQ-emotional functioning reached conceptual similarity with NCSI dyspnoea emotions. AQLQ-environmental stimuli did not reach conceptual similarity with any NCSI sub-domain.
      Nor the ACQ or domains of the AQLQ did show conceptual similarity with the NCSI sub-domains fatigue, behavioural impairment, general QoL, health-related QoL, and satisfaction with relations. The NCSI, ACQ, and AQOLQ were not significantly related to FEV1, FeNO, BMI.

      Discussion

      The present study shows that the Nijmegen Clinical Screening Instrument (NCSI) measures more aspects of health status than the Asthma Control Questionnaire (ACQ) and the Asthma Quality of Life Questionnaire (AQLQ-S) in patients with severe asthma. All sub-domains of the NCSI proved to be relevant in this patient group.
      The main aim of this study was to evaluate the added value of the NCSI to measure aspects of health status above the frequently used disease specific instruments AQLQ and ACQ. The AQLQ and the ACQ are used in numerous studies to evaluate interventions [
      • Rijssenbeek-Nouwens L.H.
      • Fieten K.B.
      • Bron A.O.
      • Hashimoto S.
      • Bel E.H.
      • Weersink E.J.
      High-altitude treatment in atopic and nonatopic patients with severe asthma.
      ,
      • Busse W.W.
      • Wenzel S.E.
      • Meltzer E.O.
      • Kerwin E.M.
      • Liu M.C.
      • Zhang N.
      • et al.
      Safety and efficacy of the prostaglandin D2 receptor antagonist AMG 853 in asthmatic patients.
      ,
      • Mancuso C.A.
      • Choi T.N.
      • Westermann H.
      • Wenderoth S.
      • Wells M.T.
      • Charlson M.E.
      Improvement in asthma quality of life in patients enrolled in a prospective study to increase lifestyle physical activity.
      ,
      • Turner S.
      • Eastwood P.
      • Cook A.
      • Jenkins S.
      Improvements in symptoms and quality of life following exercise training in older adults with moderate/severe persistent asthma.
      ], and to describe groups of patients with asthma [
      • Chhabra S.K.
      • Chhabra P.
      Gender differences in perception of dyspnea, assessment of control, and quality of life in asthma.
      ]. These studies have provided important information about the experienced symptoms, activity limitations, emotional functioning, and impact of environmental stimuli on these patients. However, health status most certainly comprises of more sub-domains than the four subscales covered by the AQLQ and the one subscale of the ACQ. We expected that the ten sub-domains of the NCSI probably measure the same, but certainly even more, aspects of health status than the AQLQ.
      Both the AQLQ and the NCSI measure the subjective symptoms, subjective impairment, and emotions. However, the NCSI measures also airflow, body composition and items that measure the experienced fatigue, satisfaction with life in general, mood, satisfaction with relationships and future, and sickness-related behavioural impairment that are not covered by the AQLQ and ACQ. On all eight NCSI sub-domains, measured by the questionnaire part, high proportions of patients with serious problems were found. In addition, all eight sub-domains were shown to represent conceptually distinct aspects of the patients health status, as evidenced by the low intercorrelations. Only the sub-domains subjective symptoms and subjective impairment showed conceptual similarity. The domain AQLQ activity limitation showed high inter correlations with the domains symptoms and environmental stimuli indicating that they measure similar concepts. However, the moderate correlation between symptoms and environmental stimuli indicate that these two domains measure separate concepts, thus both share different parts with the domain activity limitation. This is not surprising since the items of activity limitation measure activity limitation due to environmental stimuli and due to their asthma symptoms. Thus, the NCSI questionnaire part measures seven aspects of health status whereas the AQLQ measures three distinct aspects of health status. This suggests that, in patients with severe asthma, the NCSI is capable of providing a more complete picture of the patient's problems and needs on health status as compared to the ACQ and AQLQ.
      The present study shows that all NCSI subscales represent highly relevant sub-domains of health status in patients with severe asthma. In addition, heterogeneity was found between patients with respect to the number of sub-domains and in the combination of sub-domains on which patients experienced severe problems. Low to absent correlations were not only found between the non-physiological sub-domains of the NCSI, but also between physiological functioning and symptoms, behavioural impairment, and QoL. This is not a new phenomena, Haldar et al. [
      • Haldar P.
      • Pavord I.D.
      • Shaw D.E.
      • Berry M.A.
      • Thomas M.
      • Brightling C.E.
      • et al.
      Cluster analysis and clinical asthma phenotypes.
      ] also found that symptom perception is not always in concordance with eosinophilic airway inflammation, and concluded that both, symptoms and physiologic parameters, have to be measured to get a complete picture.
      Several limitations of the present study should be kept in mind with respect to the generalizability of the results. In this study we included a select group of patients, more specifically patients with severe asthma referred to a high-altitude inpatient pulmonary clinic. Even in this highly selected group of patients with severe asthma, marked heterogeneity was found. Which makes it feasible that this might even be more pronounced in a more general sample of patients with asthma. The moderate internal consistencies of the sub-domains of QoL are another limitation. In COPD the same problem exist, a possible explanation is that the included subscales measure different concepts, however further refinement will be necessary. One might question the adequacy of the cut-off scores for normal functioning on the sub-domains of the NCSI. Since, these cut-offs were based on a group of healthy persons matched by age and sex to a COPD study group [
      • Peters J.B.
      • Daudey L.
      • Heijdra Y.F.
      • Molema J.
      • Dekhuijzen P.N.
      • Vercoulen J.H.
      Development of a battery of instruments for detailed measurement of health status in patients with COPD in routine care: the Nijmegen Clinical Screening Instrument.
      ]. This could lead to an underestimation of problems in patients with asthma, because asthma patients are generally somewhat younger. Morroy et al. [
      • Morroy G.
      • Peters J.B.
      • van Nieuwenhof M.
      • Bor H.H.
      • Hautvast J.L.
      • van der Hoek W.
      • et al.
      The health status of Q-fever patients after long-term follow-up.
      ], found no significant differences between patients with Q-fever older and patients with Q-fever younger than 50 years on seven of eight NCSI sub-domains, patients younger than 50 years had significant higher scores on dyspnoea emotions.
      The reason for this study was the need for an instrument that would enable a detailed evaluation of the needs of patients with severe asthma and that could help to identify the factors that aggravate, complicate, or influence disease perception. The NCSI provides a detailed assessment of health status, and includes normative data, which render the patient's scores on each sub-domain clinically meaningful [
      • Peters J.B.
      • Daudey L.
      • Heijdra Y.F.
      • Molema J.
      • Dekhuijzen P.N.
      • Vercoulen J.H.
      Development of a battery of instruments for detailed measurement of health status in patients with COPD in routine care: the Nijmegen Clinical Screening Instrument.
      ]. The powerful mechanism is not the NCSI as instrument per sé, but by discussing the PatientProfileChart with the patient. The PatientProfileChart visualizes on which sub-domain a patient functions normally and on which sub-domain a patient experience severe problems. The PatientProfileChart allows the doctor and other healthcare providers to quickly identify the factors leading to disease burden by discussing the results [
      • Vercoulen J.H.
      A simple method to enable patient-tailored treatment and to motivate the patient to change behaviour.
      ]. Moreover, the discussion with the patient also facilitates shared-decision making, which has proven to be important in promoting adherence [
      • Bourdin A.
      • Halimi L.
      • Vachier I.
      • Paganin F.
      • Lamouroux A.
      • Gouitaa M.
      • et al.
      Adherence in severe asthma.
      ]. Moreover, the complexity of the balance between health status and the underlying problems and self-management capacities, may become visible in the discussion. This information may help in guiding non-pharmacological treatment since pharmacological treatment alone seems to be insufficient in patients with severe asthma [
      • Bourdin A.
      • Halimi L.
      • Vachier I.
      • Paganin F.
      • Lamouroux A.
      • Gouitaa M.
      • et al.
      Adherence in severe asthma.
      ]. In COPD this approach have been implemented in usual care since several years and has proven its clinical relevance. The next step would be to implement the NCSI in treatment of patients with severe asthma, and examine its sensitivity to change.

      Conclusions

      The present study showed that the NCSI, ACQ and AQLQ measure highly relevant aspects of health status in patients with severe asthma. However, the NCSI measures more aspects of health status that are not covered by the ACQ and AQLQ. The NCSI in combination with the PatientProfileChart might help to identify the impact on daily life, symptoms, QoL, and impairments in the individual patient with severe asthma.

      Conflicts of interest

      The authors JP, LR, KF, AB, EW and JV declare no conflict of interest. EHB received in behalf of the department of Respiratory Medicine of the Academic Medical Centre grants from the Dutch Asthma Foundation and from Novartis , GSK , and Chiesi . She received speaker fees from GSK, and consultant fees from Novartis and GSK, which were donated to the department.

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