Jornal de Pediatria - Vol. 78, Nº1, 2002 45

0021-7557/02/78-01/45

Jornal de Pediatria Copyright © 2002 by Sociedade Brasileira de Pediatria

ORIGINAL ARTICLE

Peak expiratory flow rate in the management of cystic fibrosis Paulo A.M. Camargos1, Mônica V.N.P. Queiroz2

Abstract Objective: to verify the role of peak expiratory flow, measured through portable meters, as an alternative test to assess pulmonary disease in cystic fibrosis. Methods: forty-nine patients aged five to 19 years old in stable health condition and able to perform the peak expiratory flow maneuver were included. In the same visit, Shwachman-Kulczycki score was recorded. Linear regression was used to assess the correlation between the Shwachman-Kulczycki score and the peak expiratory flow rate. A P value of 0.05 was considered to be significant. Results: a slight, but statistically significant correlation between absolute and percent values for this functional parameter and the Shwachman-Kulczycki score (r = 0.31, P = 0.02 and r = 0.30, P = 0.03, respectively) was found. Conclusions: although this correlation was statistically significant, these findings are not clinically relevant, i.e., the lung involvement in this disease should be assessed by classic pulmonary function tests, such as spirometry. J Pediatr (Rio J) 2002; 78 (1): 45-49: peak expiratory flow rate, cystic fibrosis.

Introduction Despite the systemic characteristic of cystic fibrosis (CF), involvement of the lungs is the chief cause of morbidity and mortality related to this disorder. The anatomopathological alterations can be verified as early as the first months of life with the dilation and hypertrophy of mucosal glands, which lead to the involvement of the small airways and subsequent bronchiolar obstruction, progressive

development of bronchiectasis, and progressive parenchymal destruction; this, in turn, leads to a reduction in the functional capacity of the lungs.1 Sequential evaluation of pulmonary function is thus required in CF patients and lung function tests should be carried out at least once a year to evaluate lung involvement. Hence, the availability and unrestricted access to spirometers is essential for the follow-up of patients and due quantitation of the several functional parameters.2 In Brazil, however, the lung function tests laboratories - which are costly structures that require relatively complex equipment and certified personnel - are located in reference centers in large and medium-sized cities; these circumstances require the patients to travel to these centers.

1. Associate Professor, Department of Pediatrics, School of Medicine, Universidade Federal de Minas Gerais (UFMG); Head, Pediatric Pulmonology Department, Hospital das Clínicas, teaching hospital of the Universidade Federal de Minas Gerais (UFMG). 2. Assistant Professor, Maternal-Infantile Department, Medical Sciences School, Fundação Lucas Machado. Financial support: Conselho Nacional de Desenvolvimento Científico e Tecnológico-CNPq. Manuscript received July 03 2001. Accepted for publication Oct 31 2001.

45

46 Jornal de Pediatria - Vol. 78, Nº1, 2002 Considering the increasing concern of Brazilian pediatricians in relation to CF, it is thus important to investigate alternative lung function tests that are better adapted to the situation of healthcare in the country and to the social and economical conditions of patients. Since portable peak flowmeters present low costs and proven usefulness in the monitoring of asthma, it seems important to investigate their use in CF patients. In this sense, despite the fact that these meters were used in several studies on cystic fibrosis (for example, to evaluate, prospectively, the effects of the long-acting beta2-agonist salmeterol),3 our review of the literature, limited to the past 30 years and to the keywords cystic fibrosis and peak expiratory flow, did not yield results indicating studies on the use of this parameter in lung function tests of CF patients. This application of the peak expiratory flow was probably not further elucidated since most CF studies were carried out in rich countries, whose authors are not subject to the budget, equipment, and personnel limitations of poorer countries. Such limitations were at the basis of the present study. Our objective was to assess the use of portable peak flowmeters as an alternative to spirometry in lung function tests for CF patients.

Patients and methods We carried out a cross-sectional study at the Pediatric Pulmonology Unit of the Hospital das Clínicas, teaching hospital of the Universidade Federal de Minas Gerais. Our study population included 49 patients whose diagnosis of CF was confirmed by sweat chloride (> 60 mEq/l). The literature recognizes that the correlation between the Shwachmann-Kulczycki (S-K) score and the spirometric parameters is satisfactory and at times excellent;4 thus, we prospectively obtained the S-K scores and peak expiratory flow (PEF) values of outpatients during one of their visits to the unit. The S-K score is calculated based on simple chest x-ray findings and three different clinical parameters: general activities, physical examination, and nutritional status. The findings and parameters are sub-divided into five different levels of severity which, in turn, are scored according to multiples of five from 5 (more severe) to 25 (less severe). Based on the final scores, the status of the patient is considered excellent (greater than 86), good (71 to 85), mild (56 to 70), moderate (41 to 55), or severe (less than 40). Study population We included all children and adolescents aged five to 19 years and clinically stable who were registered at the services of the hospital and able to perform the peak flowmeter test. Patients with overt exacerbation of the disease, cardiopathies, and neuromuscular and oromaxillofacial disorders were excluded from our population.

Peak expiratory flow rate... - Camargos PAM et alii

Study protocol We designed a specific, standardized protocol that contained the following variables: sex; age at diagnosis, age at evaluation of S-K score and PEF values (and S-K and PEF results); and weight and height. Final S-K scores and PEF values were obtained during routine procedures of the CF outpatient clinic by the same evaluator. Equipment For the evaluation of pulmonary function, we employed a mini-Wright peak flowmeter (Clement Clarke International, Essex, UK) with peak expiratory flows of 60 to 800 L/min. Prior to the study and according to previously described methodology,5 we validated the flowmeter with a flow volume calibrator (Jones Medical Instrument, Oakbrook, Illinois, USA). We carried out eight manual injections applying constant volume of three liters but varying flow rates, thus simulating forced expiration. The flow rates applied ranged from 200 L/min to 600 L/min. This range was supposed to include the expected flow rates according to the height for age group of the studied patients. Since the calibration showed that peak expiratory flow meter readings were overestimated, we applied the equation proposed by Miles et al.6 with the specific purpose of correcting the meter’s known inaccuracy. After correction according to the referred equation, the flowmeter readings presented a variation of 0.1 to 4.7% in comparison to the flow volume calibrator; these variations were in accordance with the European Respiratory Society7 and the American Thoracic Society8 guidelines for peak flowmeters. The same equation was later applied to correct each of the measurements obtained from our patients. The techniques for measurement of peak flow rates were carried out according to the recommendations of the European Respiratory Society,7 and the flow readings of each patient were compared to the reference values described by Polgar and Promahadt.9 Statistical analysis We calculated frequency distribution in order to describe the demographic, clinical, and functional characteristics of children and adolescents in the study. Considering that others have shown satisfactory levels of correlation between classical spirometric parameters and the S-K score,4,10,11 we carried out linear regression analysis to correlate, using Pearson’s correlation coefficient (r), the S-K score (independent variable) and the absolute and percentage values of peak expiratory flow (dependent variable). We also calculated the upper and lower limits of the 95% confidence interval for the values of “r” and for the coefficient of determination (R2). We classified the nutritional status of patients according to the National Center for Health Statistics (NCHS, USA) guidelines; significance level was established for P = 0.05.

Peak expiratory flow rate... - Camargos PAM et alii

Results Table 1 presents the descriptive characteristics of the 49 children and adolescents studied. The distributions of patients according to sex and to each of the three age groups were practically identical. Age at diagnosis indicated that only 28.6% of patients were diagnosed before age five years (median 7.2 years). The interval of time between diagnosis and measurement of peak expiratory flow and S-K score was of up to five years in 57.1% of patients. In relation to the nutritional status, around 63.3% of the studied population presented weight and height less than or equal to the 10th percentile. The SK scores calculated showed that 71.5% of patients presented good to excellent clinical and radiological status (average score 82.5); these results differed from those of the pulmonary function tests, which indicated that only 36.8% of patients presented normal values - more specifically, PEF greater than or equal to 80% of predicted normal value. However, the overall analysis indicated that the average (76.5% of predicted normal value) and the median (73% of predicted normal value) PEF values were close to the average S-K score (82.50). Figure 1 presents the dispersion diagram for the S-K scores and PEF values; the latter is expressed in the form of percent predicted normal value. Results indicated r = 0.30 (95% CI 0.03-0.54) and a statistically significant correlation between the S-K score and PEF value (P = 0.03). However, the coefficient of determination (R2 = 0.09) showed that linear regression explained only 9% of the variance. Figure 2 presents the absolute peak expiratory flow values. Results were similar to those above, more specifically, r = 0.31 (9%% CI 0.04-0.55) and R2 = 0.13, thus showing that linear regression explained only 13% of the variance. The correlation between the two variables was again statistically significant (P = 0.02). Table 2 presents the correlation coefficient (r) results and the respective 95% confidence intervals for the different cutoff points of the S-K score. Independently of the interval considered, the values for “r” show that the PEF does not precisely diagnose the severity of the clinical and radiological involvement of the lungs.

Discussion One of the few studies on the role of PEF in relation to CF dates back to the late 1960s. In 1969, Mellins12 compared the forced expiratory volume in one second (FEV1) with the PEF of healthy and CF children. In a comparison with spirometry, the author showed that a significant decrease in FEV1 did not correspond to that indicated by the PEF.

Jornal de Pediatria - Vol. 78, Nº1, 2002 47

Most studies compare the several scoring systems and the spirometric tests used to verify the severity of respiratory disorders. These comparisons have usually yielded uniform results. For example, studies have reported similar results for forced vital capacity (r = 0.69) and FEV1 (r = 0.67) in two different populations, adding up to 121 patients.10,13

Table 1 -

Descriptive characteristics of the analyzed patients (n=49)

Characteristics

n

%

Gender Male Female

25 24

51.0 49.0

Current age (years old) 90

- 0.11

-0.54 to 0.36

> 80

0.28

-0.09 to 0.58

> 70

0.26

-0.08 to 0.54

> 60

0.26

-0.08 to 0.54

> 50

0.26

-0.03 to 0.50

> 40

0.22

-0.07 to 0.47

> 65 to 90

0.22

-0.07 to 0.47

< 65

0.23

-0.88 to 0.71

* 95%CI: confidence interval at 95%

Beier et al. reported even higher correlation coefficients for the FEV1 (r2 = 0.72) and the vital capacity (r2 = 0.86), which are two classical spirometric parameters, and the SK score in a study with 20 cystic fibrosis patients aged eight to 18 years.14 Moreover, the difference between the PEF measured by a spirometer and the FEV1 was also demonstrated by Orenstein et al.15 while analyzing the correlation of these two measures with the Quality of Wellbeing scale (QWB); their results were r = 0.40 (P < 0.01) for the correlation with PEF and r = 0.55 (P < 0.001) for that with FEV1. Still, others have also studied the measurement of PEF through both spirometry and portable meters to assess the impact of physical and recreational activities on the pulmonary function of 58 CF patients.16 In the referred study, the authors did not assess the correlation between the scoring system and PEF. However, they did observe a clear discrepancy between the PEF measured by spirometry and by portable meters.

parameter. Though our findings indicated statistically significant correlations (Figures 1 and 2; Table 2), they are inferior in comparison to those obtained in conventional spirometry. Consequently, our results lack clinical importance, since the changes associated with PEF are chiefly the result of proximal airways involvement, which occurs at a later stage of the disease. Further, the measurement of PEF is effort-dependent2 and thus the involvement of muscle mass and strength due to chronic malnutrition2,17 and the recurring episodes of infectious exacerbations - two events that are part of the clinical status of CF - can determine variations in the PEF that may not necessarily correspond to the actual severity of the respiratory disorder.2

Taking into account previous findings that indicate satisfactory intra- and interobserver correlations for the SK score4 and for that with spirometric parameters,4,10,13-15 we were not able to show similar results for the PEF

Finally, our results suggest that PEF measures do not reliably indicate the severity of lung function involvement or the clinical and radiological involvement; thus, the PEF is neither a dependable alternative nor an acceptable marker for the evaluation of lung function in CF.

Figure 2 - Linear regression between the absolute values for peak expiratory flow and Shwachman-Kulczycki score

Acknowledgments We would like to thank professors José Dirceu Ribeiro from the Department of Pediatrics, Medical Sciences School, Universidade de Campinas (UNIVAMP) and Luciano Amedée Peret from the Department of Pediatrics, School of Medicine, Universidade Federal de Minas Gerais (UFMG) for their comments on one of the latter versions of this paper. We would also like to thank Doctor Ricardo Marques Dias, Professor and Head of the Lung Function Laboratory, Hospital Graffrée e Guinle, Universidade do Rio de Janeiro, for carrying out tests that gauged the PEF meter.

Peak expiratory flow rate... - Camargos PAM et alii

References 1. Bush A. Cardiopulmonary physiology. In: Hodson ME, Geddes DM, eds. Cystic Fibrosis. 1st ed. London: Chapman & Hall; 1995.p.151-77. 2. Brand PLP, van der Ent CK. The practical application and interpretation of simple lung function tests in cystic fibrosis. J R Soc Med 1999;92(Suppl. 37):2-12. 3. Bargon J, Viel K, Dauletbaev N. Short-term effects of regular salmeterol treatment on adult cystic fibrosis patients. Eur Respir J 1997;10:2307-11. 4. MacLusky I, Levison H. Cystic fibrosis. In: Chernick V, ed. Kendig’s Disorders of the respiratory tract in children. 6th ed. Philadelphia: WB Saunders;1998.p. 851. 5. Ruchkys VC, Dias RM, Sakurai E, Camargos PAM. Acurácia de medidores do pico de fluxo expiratório (peak-flow) da marca MiniWright. J Pediatr (Rio J) 2000;76:447-52. 6. Miles JF, Tunnicliffe W, Cayton RM, Ayres JG, Miller MR. Potential effects of correction of inaccuracies of the miniWright peak expiratory flow meter on the use of an asthma selfmanagement plan. Thorax 1996;51:403-6. 7. Quanjer PH, Lebowitz MD, Gregg I, Miller MR, Pedersen OF. Peak expiratory flow: conclusions and recommendations of a Working Party of the European Respiratory Society. Eur Respir J 1997;10(Suppl. 24):2s-8s. 8. American Thoracic Society. Standardization of spirometry: 1994 update. Am J Respir Care Med 1995;152:1107-36. 9. Polgar G, Promadhat V. Pulmonary function testing in children: techniques and standards. Philadelphia: WB Saunders;1971. 10. Lewiston N, Moss R, Hindi R, Rubinstein S, Sullivan M. Interobserver variance in clinical scoring for cystic fibrosis. Chest 1987;91:878-82.

Jornal de Pediatria - Vol. 78, Nº1, 2002 49 11. Shwachman H, Kulczycki L. Long term study of 105 patients with cystic fibrosis: studies made over a five to fourteen year period. AJDC 1958:96:6-15. 12. Mellins RB. The site of airway obstruction in cystic fibrosis. Pediatrics 1969;44:315-18. 13. Featherby EA, Weng TR, Crozier DN, Duic A, Reilly BJ, Levison H. Dynamic and static volumes, blood gas tensions, and diffusing capacity in patients with cystic fibrosis. Am Rev Respir Dis 1970;102:737-49. 14. Beier FR, Renzetti Jr AD, Mitchell M, Watanabe S. Pulmonary pathophysiology in cystic fibrosis. Am Rev Respir Dis 1966;94:430-40. 15. Orenstein DM, Nixon PA, Ross EA, Kaplan RM. The quality of well-being in cystic fibrosis. Chest 1989;95:344-47. 16. Kaplan TA, McKey, Jr RM, Toraya N, Moccia G. Impact of CF summer camp. Clin Pediatr 1992; 31:161-67. 17. Primhak RA, Coates FS. Malnutrition and peak expiratory flow rate. Eur Respir J 1988;1:801.

Correspondence Prof. Paulo Augusto Moreira Camargos Depto. de Pediatria da Faculdade de Medicina da UFMG Avenida Alfredo Balena, 190 – Sala 4061 CEP 30130-100 – Belo Horizonte, MG, Brazil Phone: + 55 31 3248.9772 – Fax: + 55 31 3248.9664 E-mail: [email protected]