title: Long-term multicentre trial in chronic nonspecific lung disease: methodology and baseline assessment in adult patients. Dutch CNSLD Study Group.
abstract: Airways obstruction and airways hyperresponsiveness are two dominant features in patients with chronic nonspecific lung disease (asthma and chronic obstructive pulmonary disease (COPD)). We set up a study to determine whether long-term (3 yrs) therapeutic intervention directed at airways obstruction and hyperresponsiveness is superior to one directed at airways obstruction alone. Patients were selected on functional criteria (age, baseline forced expiratory volume in one second (FEV1), and airways hyperresponsiveness) and, furthermore, extensively characterized by history, smoking habits, allergy, reversibility of airways obstruction and quality of life. The methodology and practical problems of setting up this large multicentre study are outlined, together with an analysis of baseline data. Standardization of methods and techniques and recruitment of patients required much effort, recruitment taking about twice as long as expected. A 3 month feasibility study allowed us to eliminate minor problems in the protocol. Over a 16 month period, 274 adult patients (18-60 yrs) from the out-patient clinics of six university centres entered the study; 99 met the diagnostic criteria for asthma, 51 for COPD, 88 for asthmatic bronchitis, and 36 could not be classified. Their mean (SD) FEV1% pred was 65.1 (15.2)%. Their geometric mean provoking concentration of histamine producing a 20% fall in FEV1 (PC20 histamine) was 0.28 mg.ml-1. In a multiple regression analysis, more severe airways hyperresponsiveness was associated with lower prechallenge FEV1% pred (p less than 0.0001), higher pack-years of smoking (p = 0.0099), blood eosinophil count (p = 0.0004), skin test reactivity (p = 0.0047) and with female sex (p = 0.0302). We conclude that setting up long-term multicentre trials in chronic nonspecific lung disease (CNSLD) is feasible and that these may offer valuable information on treatment and outcome of the disease.
authors.affiliation: Dept of Pulmonology, University Hospital, Groningen, The Netherlands.
authors.forename: P L
authors.initials: PL
authors.lastname: Brand
authors.forename: H A
authors.initials: HA
authors.lastname: Kerstjens
authors.forename: D S
authors.initials: DS
authors.lastname: Postma
authors.forename: P J
authors.initials: PJ
authors.lastname: Sterk
authors.forename: P H
authors.initials: PH
authors.lastname: Quanjer
authors.forename: H J
authors.initials: HJ
authors.lastname: Sluiter
authors.forename: J H
authors.initials: JH
authors.lastname: Dijkman
authors.forename: C L
authors.initials: CL
authors.lastname: van Herwaarden
authors.forename: C
authors.initials: C
authors.lastname: Hilvering
authors.forename: H M
authors.initials: HM
authors.lastname: Jansen
mesh_terms: D000328:Adult; D001249:Asthma / Q000188:drug therapy / Q000503:physiopathology; D001507:Beclomethasone / Q000494:pharmacology / Q000627:therapeutic use*; D016535:Bronchial Hyperreactivity / Q000188:drug therapy; D004311:Double-Blind Method; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D009241:Ipratropium / Q000494:pharmacology / Q000627:therapeutic use*; D008173:Lung Diseases, Obstructive / Q000188:drug therapy*; D008875:Middle Aged; D015337:Multicenter Studies as Topic / Q000379:methods; D010865:Pilot Projects; D012044:Regression Analysis; D013726:Terbutaline / Q000494:pharmacology / Q000627:therapeutic use*; D013997:Time Factors; D014109:Total Lung Capacity / Q000187:drug effects
chemical_list: D009241:Ipratropium; D001507:Beclomethasone; D013726:Terbutaline