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. 2005 May;60(5):395–400. doi: 10.1136/thx.2004.039230

Reproducibility of non-specific bronchial challenge in adults: implications for design, analysis and interpretation of clinical and epidemiological studies

S Chinn 1, J Schouten 1
PMCID: PMC1758909  PMID: 15860715

Abstract

Background: Poor reproducibility of an outcome measure reduces power and, in an independent variable, biases results. The intraclass correlation coefficient measures loss of power and degree of bias. Information is lacking on the intraclass correlation coefficient for bronchial responsiveness and factors affecting reproducibility.

Methods: Papers containing information on reproducibility of bronchial responsiveness were identified using a Medline search and citations. Within and between person components of variance of PD20 or PC20 were expressed in doubling dose or concentration units, and the intraclass correlation coefficient calculated when not reported.

Results: Results were extracted from 32 papers. Intraclass correlation coefficients were over 0.9 in short term studies of highly selected asthmatic patients, but larger and most long term studies had lower intraclass correlation coefficients, less than 0.5 in some cases, due to greater within person or lower between person variation. Reproducibility of dose or concentration-response slope was generally higher, but still less than that of forced expiratory volume in 1 second.

Conclusions: Information is available to calculate sample size for studies with bronchial responsiveness as the outcome, but results when bronchial responsiveness is an explanatory variable may be misleading.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abramson M. J., Saunders N. A., Hensley M. J. Analysis of bronchial reactivity in epidemiological studies. Thorax. 1990 Dec;45(12):924–929. doi: 10.1136/thx.45.12.924. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Beach J. R., Stenton S. C., Connolly M. J., Walters E. H., Hendrick D. J. Effects of diurnal variation and prolonged refractoriness on repeated measurements of airways responsiveness to methacholine. Thorax. 1995 Mar;50(3):235–239. doi: 10.1136/thx.50.3.235. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Beach J. R., Young C. L., Avery A. J., Stenton S. C., Dennis J. H., Walters E. H., Hendrick D. J. Measurement of airway responsiveness to methacholine: relative importance of the precision of drug delivery and the method of assessing response. Thorax. 1993 Mar;48(3):239–243. doi: 10.1136/thx.48.3.239. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Beckett W. S., Pace P. A., Sferlazza S. J., Carey V. J., Weiss S. T. Annual variability in methacholine responsiveness in nonasthmatic working adults. Eur Respir J. 1997 Nov;10(11):2515–2521. doi: 10.1183/09031936.97.10112515. [DOI] [PubMed] [Google Scholar]
  5. Bland J. M., Altman D. G. A note on the use of the intraclass correlation coefficient in the evaluation of agreement between two methods of measurement. Comput Biol Med. 1990;20(5):337–340. doi: 10.1016/0010-4825(90)90013-f. [DOI] [PubMed] [Google Scholar]
  6. Bland J. M., Altman D. G. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet. 1986 Feb 8;1(8476):307–310. [PubMed] [Google Scholar]
  7. Britton J., Mortagy A., Tattersfield A. Histamine challenge testing: comparison of three methods. Thorax. 1986 Feb;41(2):128–132. doi: 10.1136/thx.41.2.128. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Chinn S., Britton J. R., Burney P. G., Tattersfield A. E., Papacosta A. O. Estimation and repeatability of the response to inhaled histamine in a community survey. Thorax. 1987 Jan;42(1):45–52. doi: 10.1136/thx.42.1.45. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Chinn S., Burney P. G., Britton J. R., Tattersfield A. E., Higgins B. G. Comparison of PD20 with two alternative measures of response to histamine challenge in epidemiological studies. Eur Respir J. 1993 May;6(5):670–679. [PubMed] [Google Scholar]
  10. Chinn S. Methodology of bronchial responsiveness. Thorax. 1998 Nov;53(11):984–988. doi: 10.1136/thx.53.11.984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Cockcroft D. W., Berscheid B. A., Murdock K. Y. Measurement of responsiveness to inhaled histamine using FEV1: comparison of PC20 and threshold. Thorax. 1983 Jul;38(7):523–526. doi: 10.1136/thx.38.7.523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Cockcroft D. W., Berscheid B. A., Murdock K. Y. Unimodal distribution of bronchial responsiveness to inhaled histamine in a random human population. Chest. 1983 May;83(5):751–754. doi: 10.1378/chest.83.5.751. [DOI] [PubMed] [Google Scholar]
  13. Connolly M. J., Avery A. J., Walters E. H., Hendrick D. J. The relationship between bronchial responsiveness to methacholine and bronchial responsiveness to histamine in asthmatic subjects. Pulm Pharmacol. 1988;1(1):53–58. doi: 10.1016/0952-0600(88)90011-7. [DOI] [PubMed] [Google Scholar]
  14. Connolly M. J., Kelly C., Walters E. H., Hendrick D. J. An assessment of methacholine inhalation tests in elderly asthmatics. Age Ageing. 1988 Mar;17(2):123–128. doi: 10.1093/ageing/17.2.123. [DOI] [PubMed] [Google Scholar]
  15. Cook N. R., Kumanyika S. K., Cutler J. A. Effect of change in sodium excretion on change in blood pressure corrected for measurement error. The Trials of Hypertension Prevention, Phase I. Am J Epidemiol. 1998 Sep 1;148(5):431–444. doi: 10.1093/oxfordjournals.aje.a009668. [DOI] [PubMed] [Google Scholar]
  16. Dehaut P., Rachiele A., Martin R. R., Malo J. L. Histamine dose-response curves in asthma: reproducibility and sensitivity of different indices to assess response. Thorax. 1983 Jul;38(7):516–522. doi: 10.1136/thx.38.7.516. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Dyer A. R., Elliott P., Shipley M. Urinary electrolyte excretion in 24 hours and blood pressure in the INTERSALT Study. II. Estimates of electrolyte-blood pressure associations corrected for regression dilution bias. The INTERSALT Cooperative Research Group. Am J Epidemiol. 1994 May 1;139(9):940–951. doi: 10.1093/oxfordjournals.aje.a117100. [DOI] [PubMed] [Google Scholar]
  18. Frew A. J., Kennedy S. M., Chan-Yeung M. Methacholine responsiveness, smoking, and atopy as risk factors for accelerated FEV1 decline in male working populations. Am Rev Respir Dis. 1992 Oct;146(4):878–883. doi: 10.1164/ajrccm/146.4.878. [DOI] [PubMed] [Google Scholar]
  19. Gibbons W. J., Sharma A., Lougheed D., Macklem P. T. Detection of excessive bronchoconstriction in asthma. Am J Respir Crit Care Med. 1996 Feb;153(2):582–589. doi: 10.1164/ajrccm.153.2.8564102. [DOI] [PubMed] [Google Scholar]
  20. Hedman J., Alanko K., Nieminen M. M. Repeatability of a rapid dosimetric method for methacholine challenge using a pocket turbine spirometer for FEV1 measurements. Clin Physiol. 1996 Jul;16(4):353–359. doi: 10.1111/j.1475-097x.1996.tb00724.x. [DOI] [PubMed] [Google Scholar]
  21. Higgins B. G., Britton J. R., Chinn S., Jones T. D., Vathenen A. S., Burney P. G., Tattersfield A. E. Comparison of histamine and methacholine for use in bronchial challenge tests in community studies. Thorax. 1988 Aug;43(8):605–610. doi: 10.1136/thx.43.8.605. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Juniper E. F., Frith P. A., Dunnett C., Cockcroft D. W., Hargreave F. E. Reproducibility and comparison of responses to inhaled histamine and methacholine. Thorax. 1978 Dec;33(6):705–710. doi: 10.1136/thx.33.6.705. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Juniper E. F., Frith P. A., Hargreave F. E. Long-term stability of bronchial responsiveness to histamine. Thorax. 1982 Apr;37(4):288–291. doi: 10.1136/thx.37.4.288. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Knox A. J., Coleman H. E., Britton J. R., Tattersfield A. E. A comparison of three measures of the response to inhaled methacholine. Eur Respir J. 1989 Sep;2(8):736–740. [PubMed] [Google Scholar]
  25. Knox A. J., Wisniewski A., Cooper S., Tattersfield A. E. A comparison of the Yan and a dosimeter method for methacholine challenge in experienced and inexperienced subjects. Eur Respir J. 1991 Apr;4(4):497–502. [PubMed] [Google Scholar]
  26. Löwhagen O., Lindholm N. B. Short-term and long-term variation in bronchial response to histamine in asthmatic patients. Eur J Respir Dis. 1983 Aug;64(6):466–472. [PubMed] [Google Scholar]
  27. Madsen F., Rathlou N. H., Frølund L., Svendsen U. G., Weeke B. Short and long term reproducibility of responsiveness to inhaled histamine: Rt compared to FEV1 as measurement of response to challenge. Eur J Respir Dis. 1985 Sep;67(3):193–203. [PubMed] [Google Scholar]
  28. Neild J. E., Twort C. H., Chinn S., McCormack S., Jones T. D., Burney P. G., Cameron I. R. The repeatability and validity of respiratory resistance measured by the forced oscillation technique. Respir Med. 1989 Mar;83(2):111–118. doi: 10.1016/s0954-6111(89)80224-0. [DOI] [PubMed] [Google Scholar]
  29. O'Connor G., Sparrow D., Taylor D., Segal M., Weiss S. Analysis of dose-response curves to methacholine. An approach suitable for population studies. Am Rev Respir Dis. 1987 Dec;136(6):1412–1417. doi: 10.1164/ajrccm/136.6.1412. [DOI] [PubMed] [Google Scholar]
  30. Oldham P. D., Cole T. J. Estimation of the FEV. Thorax. 1983 Sep;38(9):662–667. doi: 10.1136/thx.38.9.662. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Peat J. K., Unger W. R., Combe D. Measuring changes in logarithmic data, with special reference to bronchial responsiveness. J Clin Epidemiol. 1994 Oct;47(10):1099–1108. doi: 10.1016/0895-4356(94)90096-5. [DOI] [PubMed] [Google Scholar]
  32. Rijcken B., Schouten J. P., Weiss S. T., Meinesz A. F., de Vries K., van der Lende R. The distribution of bronchial responsiveness to histamine in symptomatic and in asymptomatic subjects. A population-based analysis of various indices of responsiveness. Am Rev Respir Dis. 1989 Sep;140(3):615–623. doi: 10.1164/ajrccm/140.3.615. [DOI] [PubMed] [Google Scholar]
  33. Rijcken B., Schouten J. P., Weiss S. T., Rosner B., De Vries K., Van der Lende R. Long-term variability of bronchial responsiveness to histamine in a random population sample of adults. Am Rev Respir Dis. 1993 Oct;148(4 Pt 1):944–949. doi: 10.1164/ajrccm/148.4_Pt_1.944. [DOI] [PubMed] [Google Scholar]
  34. Rijcken B., Schouten J. P., Xu X., Rosner B., Weiss S. T. Airway hyperresponsiveness to histamine associated with accelerated decline in FEV1. Am J Respir Crit Care Med. 1995 May;151(5):1377–1382. doi: 10.1164/ajrccm.151.5.7735588. [DOI] [PubMed] [Google Scholar]
  35. Ruffin R. E., Alpers J. H., Crockett A. J., Hamilton R. Repeated histamine inhalation tests in asthmatic patients. J Allergy Clin Immunol. 1981 Apr;67(4):285–289. doi: 10.1016/0091-6749(81)90023-3. [DOI] [PubMed] [Google Scholar]
  36. Ryan G., Dolovich M. B., Roberts R. S., Frith P. A., Juniper E. F., Hargreave F. E., Newhouse M. T. Standardization of inhalation provocation tests: two techniques of aerosol generation and inhalation compared. Am Rev Respir Dis. 1981 Feb;123(2):195–199. doi: 10.1164/arrd.1981.123.2.195. [DOI] [PubMed] [Google Scholar]
  37. Schouten J. P., Tager I. B. Interpretation of longitudinal studies. An overview. Am J Respir Crit Care Med. 1996 Dec;154(6 Pt 2):S278–S284. doi: 10.1164/ajrccm/154.6_Pt_2.S278. [DOI] [PubMed] [Google Scholar]
  38. Seppälä O. P. A method for measuring the effects of anticholinergics on histamine-induced bronchoconstriction in normal subjects. Oxitropium bromide provides dose-dependent protection. Respir Med. 1994 Apr;88(4):273–279. doi: 10.1016/0954-6111(94)90056-6. [DOI] [PubMed] [Google Scholar]
  39. Seppälä O. P. The dose-response slope: a useful method for expressing the results of methacholine provocation tests in healthy subjects? Respir Med. 1991 Sep;85(5):365–371. doi: 10.1016/s0954-6111(06)80179-4. [DOI] [PubMed] [Google Scholar]
  40. Sovijärvi A. R., Malmberg L. P., Reinikainen K., Rytilä P., Poppius H. A rapid dosimetric method with controlled tidal breathing for histamine challenge. Repeatability and distribution of bronchial reactivity in a clinical material. Chest. 1993 Jul;104(1):164–170. doi: 10.1378/chest.104.1.164. [DOI] [PubMed] [Google Scholar]
  41. Sundblad B. M., Malmberg P., Larsson K. Comparison of airway conductance and FEV(1) as measures of airway responsiveness to methacholine. Discrimination of small differences in bronchial responsiveness with Gaw and FEV(1). Clin Physiol. 2001 Nov;21(6):673–681. doi: 10.1046/j.1365-2281.2001.00372.x. [DOI] [PubMed] [Google Scholar]
  42. Tosteson T. D., Buonaccorsi J. P., Demidenko E. Covariate measurement error and the estimation of random effect parameters in a mixed model for longitudinal data. Stat Med. 1998 Sep 15;17(17):1959–1971. doi: 10.1002/(sici)1097-0258(19980915)17:17<1959::aid-sim886>3.0.co;2-f. [DOI] [PubMed] [Google Scholar]
  43. Trigg C. J., Jhalli N., Herdman M. J., Cundell D. R., Thomas J. M., Davies R. J. The daily variability of bronchial responsiveness to methacholine. Eur Respir J. 1990 Sep;3(8):867–871. [PubMed] [Google Scholar]
  44. Trigg C. J., Tooley M., D'Souza M. F., Herdman M. J., Thomas J. M., Davies R. J. Factors affecting the long-term variability of bronchial responsiveness in an adult general practice population. Eur Respir J. 1994 Apr;7(4):703–709. doi: 10.1183/09031936.94.07040703. [DOI] [PubMed] [Google Scholar]
  45. Van Schayck C. P., Dompeling E., Van Herwaarden C. L., Wever A. M., Van Weel C. Interacting effects of atopy and bronchial hyperresponsiveness on the annual decline in lung function and the exacerbation rate in asthma. Am Rev Respir Dis. 1991 Dec;144(6):1297–1301. doi: 10.1164/ajrccm/144.6.1297. [DOI] [PubMed] [Google Scholar]
  46. Wood-Baker R., Town G. I., Benning B., Holgate S. T. The reproducibility and effect on non-specific airway responsiveness of inhaled prostaglandin D2 and leukotriene D4 in asthmatic subjects. Br J Clin Pharmacol. 1995 Feb;39(2):119–123. doi: 10.1111/j.1365-2125.1995.tb04417.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Yan K., Salome C., Woolcock A. J. Rapid method for measurement of bronchial responsiveness. Thorax. 1983 Oct;38(10):760–765. doi: 10.1136/thx.38.10.760. [DOI] [PMC free article] [PubMed] [Google Scholar]

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