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Does earlier lobectomy result in better long-term pulmonary function in children with congenital lung anomalies?
Journal of Pediatric Surgery (2012) 47, 852–856
www.elsevier.com/locate/jpedsurg
Does earlier lobectomy result in better long-term pulmonary function in children with congenital lung anomalies? A prospective study Yoko Naito a , Alana Beres b , Eveline Lapidus-Krol b , Felix Ratjen a , Jacob C. Langer b,⁎ a
Division of Respirology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada M5G 1X8 Division of General and Thoracic Surgery, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada M5G 1X8 b
Received 6 January 2012; accepted 26 January 2012
Key words: Congenital pulmonary airway malformation; Lobectomy; Pulmonary function test; Cardiopulmonary exercise test
Abstract Background: Management of asymptomatic congenital pulmonary airway malformations remains controversial when addressing the optimal timing of surgical resection. Neonatal resection is advocated by some based on the theory that earlier lobectomy results in greater compensatory lung growth. We examined whether age at lobectomy is correlated with better pulmonary outcomes as reflected by pulmonary function and exercise testing. Methods: Patients who had lobectomy for congenital pulmonary airway malformation between 1985 and 2002 were identified and underwent detailed clinical history, physical examination, pulmonary function testing (total lung capacity, forced vital capacity, forced expiratory volume in 1 second), and exercise testing (power, maximal oxygen uptake [VO2max]). Results: Of 87 patients identified, 47 met the inclusion criteria, and 28 were tested prospectively. Age at the time of lobectomy ranged from 3 days to 56 months. There was no correlation between age at lobectomy and pulmonary function (total lung capacity, P = .408; forced vital capacity, P = .319; forced expiratory volume in 1 second, P = .174) or maximal work capacity (power, P = .280). There was a trend toward lower VO2max in patients who had undergone lobectomy at an older age (VO2max, P = .055). Conclusion: Most children undergoing lobectomy have normal long-term pulmonary function. We found no correlation between age at lobectomy and future pulmonary function. Cardiopulmonary exercise testing should be considered in evaluating functional outcome in these patients. © 2012 Elsevier Inc. All rights reserved.
Congenital pulmonary airway malformations (CPAMs) are characterized by abnormal lung formation during fetal life, which results in a cystic malformation involving part or ⁎ Corresponding author. Tel.: +1 416 813 7340; fax: +1 416 813 7477. E-mail address: [email protected] (J.C. Langer). 0022-3468/$ – see front matter © 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.jpedsurg.2012.01.037
all of a pulmonary lobe. These lesions occur between 1 in 10,000 and 1 in 35,000 live births [1,2] and are increasingly being diagnosed prenatally by ultrasound [3]. Some fetal CPAMs grow rapidly and result in hydrops and fetal death, but most remain stable or decrease in size and are often asymptomatic at birth.
Earlier lobectomy in children with congenital lung anomalies Whether or not lobectomy should be done routinely for asymptomatic CPAM is controversial, and the optimal timing of surgery has not been established [3-7]. Early lobectomy has been suggested by some to avoid the potential development of complications such as: recurrent infections, pneumothoraces, or even the rare development of lung malignancy [2,8-12]. Balanced against this are the risks of lobectomy, which include bleeding, infection, chest wall deformity, and risks associated with general anesthesia [13,14]. Early routine lobectomy has been advocated by some surgeons based on the presumption that compensatory lung growth is more complete if the lobectomy is performed as early as possible. Arguments have been made regarding the fact that delaying the lobectomy until later childhood increases the risk of infection and may result in less or no compensatory lung growth [15,16]. However, anecdotal reports suggest that the relationship between timing of lobectomy and degree of compensatory lung growth remains unclear [17,18]. In this study, we sought to prospectively examine whether age at lobectomy is correlated with functional outcome, as reflected by pulmonary function and exercise testing.
1. Methods Patients who underwent lobectomy for benign cystic lung disease between 1985 and 2002 were identified through health records at the Hospital for Sick Children. All patients were considered for enrollment from this list if they met the inclusion criteria. The inclusion and exclusion criteria are listed below: Inclusion criteria are as follows: 1. A patient who underwent previous lobectomy for suspected CPAM 2. A Patient who is 8 to 23 years old at the time of enrollment 3. A patient who is able to perform body plethysmography 4. A patient who is able to perform exercise testing 5. A patient or parent who can complete questionnaires Exclusion criteria are as follows 1. Patients with underlying diffuse lung disease (eg, cystic fibrosis) 2. A patient who had underwent surgical procedure of the thorax other than lobectomy (eg pneumonectomy or partial lobectomy) 3. Refusal to consent to participate Patients who met the inclusion criteria and who signed a consent form underwent a detailed clinical history and physical examination, pulmonary function, and cardiopulmonary exercise testing. Total lung capacity (TLC), forced vital capacity (FVC), and forced expiratory volume in 1
853 second (FEV1) were used as indicators of pulmonary growth. Measures below 80% predicted were considered to represent impaired pulmonary function. Maximal work capabilities (power) and maximal oxygen uptake (VO2max) were determined by cardiopulmonary exercise testing. The results obtained from the patients were compared with the normal reference based on sex and body surface area [19]. Statistical analysis was performed using Student t test, χ2 test, and analysis of variance test, with a P b .05 considered significant. Multivariate statistical analysis with logistic regression was used to assess the effect of various factors on pulmonary function and exercise capacities. The SPSS version 16.0 was used to perform the statistical analyses (SPSS, Chicago, IL). The study was approved by the Research Ethics Board of The Hospital for Sick Children, Ontario, Canada (No. 1000013651).
2. Results A total of 87 patients were identified through health records. Forty patients were excluded from the study because they did not meet the inclusion criteria or declined to participate. Forty-seven patients met the inclusion criteria, and study packages containing a study invitation letter and a research consent form were sent by mail. We then attempted to contact parents or patients via telephone to follow-up. Patients who agreed to participate then came for a clinic visit, which included a detailed clinical history, physical examination, pulmonary function testing, and cardiopulmonary exercise testing. Of the 47 patients, 28 agreed to participate and were prospectively tested. Twelve patients could not be contacted, and 7 were either too busy or lived too far to come for testing (Fig. 1). Of 28 patients in the study population, 12 were male and 16 were female. The mean age at the time of lobectomy was 13 months (range, 3 days to 56 months). Nineteen patients (68%) had an antenatal diagnosis. Thirteen patients (46.4%) were asymptomatic before lobectomy. There were complications in 5 patients: 2 with persistent pneumothoraces and 3 with atelectasis. All patients underwent thoracotomy. The distribution of the types of operation was as follows: 8 right upper lobectomy, 10 right lower lobectomy, 4 left upper lobectomy, and 6 left lower lobectomy. Twenty-six patients (92%) had a CPAM, 1 patient (4%) had an intralobar sequestration, and 1 patient (4%) had chronic pneumonia confirmed on pathology. The mean follow-up age of the participants was 12.8 years (range, 8-18 years). Twenty-eight patients underwent pulmonary function testing, and 27 patients underwent cardiopulmonary exercise testing (Table 1). The mean TLC was 96% predicted, the mean FVC was 90% predicted, and the mean FEV1 was 82% predicted. Five patients (18.5%) had FVC lower than 80% predicted, and 13 patients (46.4%) had FEV1 lower than 80% predicted. There was no correlation between age at
854
Y. Naito et al.
Assessed for Eligibility n = 87 Eligible n = 47 (54%)
Not eligible n = 40 (46%) Not meeting inclusion criteria* n = 37 Declined to participate n = 3 (6%)
Not Recruited n = 19 (40%)
Recruited n = 28 (60%)
Unable to contact n = 12 (24%)
Completed Study Follow-up
Unable to come n = 7 (14%)
n = 28
Exercise Test n = 27
Pulmonary Function Test n = 28
Analyzed n = 28
Fig. 1 Flow diagram of participants. Eighty-seven patients were identified through health records. Forty patients were excluded from the study. Forty-seven patients met the inclusion criteria, and 28 agreed to participate. ⁎Surgery other than lobectomy (n = 22): partial lobectomy (n = 4), cyst resection (n = 8), wedge resection (n = 3), lung cancer (n = 1), more than 1 lobectomy (n = 3), and no surgery (n = 3). Diagnosis other than CPAM (n = 9): neurologically impaired (n = 1), died (n = 1), cystic fibrosis (n = 1), trauma (n = 2), chronic infection (n = 1), pneumocele (n = 1), congenital diaphragmatic hernia (n = 1), and Langerhans cell histiocytosis (n = 1). Age, ≥23 years (n = 6).
lobectomy and pulmonary function (TLC, P = .408; FVC, P = .319; FEV1, P = .174), and maximal work capacity (power, P = .280) and VO2max (P = .055). Patients with right-sided lobectomies had a significantly higher TLC than those with left-sided lobectomy, but there was no significant difference in exercise capacities (TLC, P = .010; FVC, P = .201; FEV1, P = .547; power, P = .513; VO2max, P = .326). There was also no significant difference in pulmonary function and cardiopulmonary exercise capacity between males and females (TLC, P = .179; FVC, P = .365; FEV1, P = .092; power, P = .974; VO2max, P = .520), and between lobectomy of upper and lower lobes (TLC, P = .738; FVC, P = .518; FEV1, P = .435; power, P = .786; VO2max, P =
Table 1 Results of pulmonary function tests and cardiopulmonary exercise tests
TLC % predicted FVC % predicted FEV1 % predicted Power % predicted VO2max % predicted
n
Mean (SD)
Range
28 28 28 27 27
96 (15) 90 (16) 82 (17) 84 (13) 84 (16)
46-114 40-117 39-121 57-106 48-111
.117). Nine patients (32.1%) reported having a history of asthma. Four patients with and 2 patients without history of asthma were currently on either bronchodilator or bronchodilator and inhaled steroids. There was no significant difference in pulmonary function and cardiopulmonary exercise capacity between those with and without asthma (TLC, P = .304; FVC, P = .217; FEV1, P = .262; power, P = .488; VO2max, P = .399). Two patients with and 3 patients without history of asthma had an FEV1/FVC ratio lower than 80%. The mean FEV1/FVC ratio of patients with history of asthma was 91%, and there was no significant difference between those with and without history of asthma (P = .990). Three patients were found to have a mild chest wall deformity upon physical examination, and there was no significant difference in pulmonary function and cardiopulmonary exercise capacity between those with and without chest wall deformity (TLC, P = .352; FVC, P = .327; FEV1, P = .113; power, P = .108; VO2max, P = .702). The results of multiple regression analyses of the major variables (right-sided lobectomy, symptomatic before lobectomy, and age at lobectomy b24 months), using abnormal pulmonary function tests and abnormal exercise function as outcomes, are shown in Table 2. Symptomatic presentation
Earlier lobectomy in children with congenital lung anomalies Table 2
855
Predictors of abnormal pulmonary functions and abnormal exercise capacity
Variables TLC b80% predicted FVC b80% predicted FEV1 b80% predicted Power b80% predicted VO2max b80% predicted
Right sided Symptomatic Lobectomy age b24 Right sided Symptomatic Lobectomy age b24 Right sided Symptomatic Lobectomy age b24 Right sided Symptomatic Lobectomy age b24 Right sided Symptomatic Lobectomy age b24
mo
mo
mo
mo
mo
n
P
Exp(B)
95.0% CI for Exp(B) Lower
Upper
18 15 24 18 15 24 18 15 24 18 15 24 18 15 24
.371 .999 .508 .982 .907 .315 .086 .156 .605 .757 .043 .270 .053 .662 .150
3.278 3.486E8 1.032 1.026 1.149 1.069 0.166 3.981 1.015 1.344 6.837 .967 6.881 1.511 0.955
0.243 0.000 0.941 0.104 0.113 0.939 0.022 0.589 0.960 0.207 1.062 0.910 0.976 0.237 0.898
44.148 . 1.131 10.119 11.709 1.217 1.285 26.883 1.073 8.706 44.016 1.027 48.530 9.632 1.017
CI indicates confidence interval.
was associated with a decrease work capacity (P = .043; 95% confidence interval, 1.062-44.016).
3. Discussion Although there is general agreement that symptomatic CPAM should be resected, the need for routine lobectomy in children with asymptomatic CPAM remains controversial. The controversy revolves around a comparison of the risks of lobectomy with the risks of observant management, which mainly consist of infection and the possibility of malignancy. Advocates of early routine lobectomy also cite concern about decreased compensatory lung growth in children who would be initially managed nonoperatively and would then require lobectomy later in childhood or during adulthood because of infection or cancer. When we prospectively tested our patients who had lobectomy, we found no correlation between age at lobectomy and pulmonary function or maximal work capacity, which is consistent with our findings in an earlier, retrospective study [20]. We did find a trend toward lower VO2max in patients who underwent lobectomy at older age (VO2max, P = .055). This suggests that early lobectomy may benefit in future exercise tolerance in these patients. There were several other interesting findings. First, there was a trend of higher pulmonary function and exercise capacities in patients who were asymptomatic at the time of lobectomy than in those with either pneumonia, shortness of breath, or ventilatory support before lobectomy (TLC, P = .064 FVC, P = .244; FEV1, P = .496; power, P = .070; VO2max, P = .066). This may be because the CPAM in these children was smaller, or because the symptomatic group
tended to be older at the time of lobectomy. Second, patients with right-sided lobectomy had a significantly higher TLC than those with left-sided lobectomy. This may be because lobectomy on the right side leaves 2 other lobes to compensate the lost volume, whereas lobectomy on the left side leaves only 1 lobe to compensate. The number of patients having a history of asthma was 32.1% in this study and was higher than the current estimated asthma prevalence, that is, 9.6% among children 18 years or younger [21]. Although results of pulmonary function and cardiopulmonary exercise testing between those with and without history of asthma were not significantly different, the relatively low mean of FEV1 (82%) in this subgroup may suggest underlying susceptibility to asthma in this group. In the current study, details regarding asthma were not collected (eg, age of onset). In addition, the incidence of asthma in our study may be overestimated because it was based on parental information, and most of these patients having normal FEV1/FVC ratio suggests that the incidence of ongoing airway obstruction is rare. Further study is needed to investigate the relationship between asthma and CPAM, and the timing of lobectomy. A limitation of our study included difficulty in recruiting all eligible patients because many of them were unable to be contacted. Although this resulted in a relatively small sample size, which did not fully represent the entire population, it is one of the largest studies in the literature looking at long-term pulmonary function in children who underwent lobectomy. Because of the difficulty contacting the older patients, many of whom had moved, the patients who agreed to participate in the study were younger than the patients who were eligible but not recruited. The present study demonstrates that most children undergoing surgery for CPAM have normal long-term lung
856 function, regardless of the timing of lobectomy. The lack of a statistically significant effect of age at lobectomy on pulmonary function and cardiopulmonary exercise testing implies that concern about compensatory lung growth is not a valid argument for advocating early routine lobectomy in children with asymptomatic CPAM. However, the trend toward diminished VO2max in patients who underwent lobectomy at older age suggests that cardiopulmonary exercise testing should be considered when investigating pulmonary function after lobectomy. In addition, the relatively high incidence of asthma symptoms and FEV1 below the population standard suggests that a high index of suspicion for asthma should be maintained during the longterm follow-up for these children.
References [1] Duncombe GH, Dickinson JE, Kikiros CS. Prenatal diagnosis and management of congenital cystic adenomatoid malformation of the lung. Am J Obstet Gynecol 2002;187:950-4. [2] Laberge JM, Flageole H, Pugash D, et al. Outcome of prenatally diagnosed congenital cystic adenomatoid malformation: a Canadian experience. Fetal Diagn Ther 2001;16:178-86. [3] Miller JA, Corteville JE, Langer JC. Congenital cystic adenomatoid malformation in the fetus: natural history and predictors of outcome. J Pediatr Surg 1996;31:805-8. [4] Lo AY, Jones S. Lack of consensus among Canadian pediatric surgeons regarding the management of congenital cystic adenomatoid malformation of the lung. Journal of Pediatr Surg 2008;43: 797-9. [5] Nakajima C, Kijimoto C, Yokoyama Y, et al. Longitudinal follow-up of pulmonary function after lobectomy in childhood—factors affecting lung growth. Pediatr Surg Int 1998;13:341-5. [6] Khosa JK, Leong SL, Borzi PA. Congenital cystic adenomatoid malformation of the lung: indications and timing of surgery. Pediatr Surg Int 2001;20:505-8.
Y. Naito et al. [7] Calvert JK, Lakhoo K. Antenatally suspected congenital cystic adenomatoid malformation of the lung: postnatal investigation and timing of surgery. J Pediatr Surg 2007;42:411-4. [8] Adzick NS, Harrison MR, Crombleholme TM, et al. Fetal lung lesions —management and outcome. Am J Obstet Gynecol 1998;179:884-9. [9] Lujan M, Bosque M, Mirapeix RM, et al. Late-onset congenital cystic adenomatoid malformation of the lung. Respiration 2002;69:148-54. [10] Papagiannopoulus K, Hughes S, Nicholson A, et al. Cystic lung lesions in the pediatric and adult population: surgical experience at the Brompton hospital. Ann Thorac Surg 2002;73:1594-8. [11] Sitting SE, Asay GF. Congenital cystic adenomatoid malformation in the newborn: two case studies and review of the literature. Respir Care 2000;45:1188-95. [12] Zach MS, Eber E. Adult outcome of congenital lower respiratory tract malformations. Thorax 2001;56:65-72. [13] Aziz D, Langer JC, Tuuha SE, et al. Perinatally diagnosed asymptomatic congenital cystic adenomatoid malformation: to resect or not? J Pediatr Surg 2004;39:329-34. [14] van Leeuwen K, Teitelbaum DH, Hirschl RB, et al. Prenatal diagnosis of congenital cystic adenomatoid malformation and its postnatal presentation, surgical indications, and natural history. J Pediatr Surg 1999;34:794-8. [15] Bradesky G. Long-term results of pulmonary resections in childhood. Prog Pediatr Surg 1977;10:267-76. [16] Thurlbeck WM. Postnatal human lung growth. Thorax 1982;37: 564-71. [17] Frenckner B, Freyschuss U. Pulmonary function after lobectomy for congenital lobar emphysema and congenital cystic adenomatoid malformation. A follow-up study. Sccand J Thorac Cardiovasc Surg 1982;16:293-8. [18] Thurlbeck WM. Postpneumonectomy compensatory lung growth. Am Rev Respir Dis 1983;128:965-7. [19] Washington RL, van Gundy JC, Cohen C, et al. Normal aerobic and anaerobic exercise data for North American school-aged children. J Pediatr 1988;112:223-33. [20] Keijer R, Chiu PPL, Ratjen F, et al. Pulmonary function after early vs late lobectomy during childhood: a preliminary study. J Pediatr Surg 2009;44:893-5. [21] Akinbami LJ, Moorman JE, Liu X. Asthma prevalence, health care use, and mortality: United States, 2005-2009. National Health Statistics Reports 2011;32:1. www.cdc.gov/nchs/data/nhsr/nhsr032.pdf. 2011.
www.elsevier.com/locate/jpedsurg
Does earlier lobectomy result in better long-term pulmonary function in children with congenital lung anomalies? A prospective study Yoko Naito a , Alana Beres b , Eveline Lapidus-Krol b , Felix Ratjen a , Jacob C. Langer b,⁎ a
Division of Respirology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada M5G 1X8 Division of General and Thoracic Surgery, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada M5G 1X8 b
Received 6 January 2012; accepted 26 January 2012
Key words: Congenital pulmonary airway malformation; Lobectomy; Pulmonary function test; Cardiopulmonary exercise test
Abstract Background: Management of asymptomatic congenital pulmonary airway malformations remains controversial when addressing the optimal timing of surgical resection. Neonatal resection is advocated by some based on the theory that earlier lobectomy results in greater compensatory lung growth. We examined whether age at lobectomy is correlated with better pulmonary outcomes as reflected by pulmonary function and exercise testing. Methods: Patients who had lobectomy for congenital pulmonary airway malformation between 1985 and 2002 were identified and underwent detailed clinical history, physical examination, pulmonary function testing (total lung capacity, forced vital capacity, forced expiratory volume in 1 second), and exercise testing (power, maximal oxygen uptake [VO2max]). Results: Of 87 patients identified, 47 met the inclusion criteria, and 28 were tested prospectively. Age at the time of lobectomy ranged from 3 days to 56 months. There was no correlation between age at lobectomy and pulmonary function (total lung capacity, P = .408; forced vital capacity, P = .319; forced expiratory volume in 1 second, P = .174) or maximal work capacity (power, P = .280). There was a trend toward lower VO2max in patients who had undergone lobectomy at an older age (VO2max, P = .055). Conclusion: Most children undergoing lobectomy have normal long-term pulmonary function. We found no correlation between age at lobectomy and future pulmonary function. Cardiopulmonary exercise testing should be considered in evaluating functional outcome in these patients. © 2012 Elsevier Inc. All rights reserved.
Congenital pulmonary airway malformations (CPAMs) are characterized by abnormal lung formation during fetal life, which results in a cystic malformation involving part or ⁎ Corresponding author. Tel.: +1 416 813 7340; fax: +1 416 813 7477. E-mail address: [email protected] (J.C. Langer). 0022-3468/$ – see front matter © 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.jpedsurg.2012.01.037
all of a pulmonary lobe. These lesions occur between 1 in 10,000 and 1 in 35,000 live births [1,2] and are increasingly being diagnosed prenatally by ultrasound [3]. Some fetal CPAMs grow rapidly and result in hydrops and fetal death, but most remain stable or decrease in size and are often asymptomatic at birth.
Earlier lobectomy in children with congenital lung anomalies Whether or not lobectomy should be done routinely for asymptomatic CPAM is controversial, and the optimal timing of surgery has not been established [3-7]. Early lobectomy has been suggested by some to avoid the potential development of complications such as: recurrent infections, pneumothoraces, or even the rare development of lung malignancy [2,8-12]. Balanced against this are the risks of lobectomy, which include bleeding, infection, chest wall deformity, and risks associated with general anesthesia [13,14]. Early routine lobectomy has been advocated by some surgeons based on the presumption that compensatory lung growth is more complete if the lobectomy is performed as early as possible. Arguments have been made regarding the fact that delaying the lobectomy until later childhood increases the risk of infection and may result in less or no compensatory lung growth [15,16]. However, anecdotal reports suggest that the relationship between timing of lobectomy and degree of compensatory lung growth remains unclear [17,18]. In this study, we sought to prospectively examine whether age at lobectomy is correlated with functional outcome, as reflected by pulmonary function and exercise testing.
1. Methods Patients who underwent lobectomy for benign cystic lung disease between 1985 and 2002 were identified through health records at the Hospital for Sick Children. All patients were considered for enrollment from this list if they met the inclusion criteria. The inclusion and exclusion criteria are listed below: Inclusion criteria are as follows: 1. A patient who underwent previous lobectomy for suspected CPAM 2. A Patient who is 8 to 23 years old at the time of enrollment 3. A patient who is able to perform body plethysmography 4. A patient who is able to perform exercise testing 5. A patient or parent who can complete questionnaires Exclusion criteria are as follows 1. Patients with underlying diffuse lung disease (eg, cystic fibrosis) 2. A patient who had underwent surgical procedure of the thorax other than lobectomy (eg pneumonectomy or partial lobectomy) 3. Refusal to consent to participate Patients who met the inclusion criteria and who signed a consent form underwent a detailed clinical history and physical examination, pulmonary function, and cardiopulmonary exercise testing. Total lung capacity (TLC), forced vital capacity (FVC), and forced expiratory volume in 1
853 second (FEV1) were used as indicators of pulmonary growth. Measures below 80% predicted were considered to represent impaired pulmonary function. Maximal work capabilities (power) and maximal oxygen uptake (VO2max) were determined by cardiopulmonary exercise testing. The results obtained from the patients were compared with the normal reference based on sex and body surface area [19]. Statistical analysis was performed using Student t test, χ2 test, and analysis of variance test, with a P b .05 considered significant. Multivariate statistical analysis with logistic regression was used to assess the effect of various factors on pulmonary function and exercise capacities. The SPSS version 16.0 was used to perform the statistical analyses (SPSS, Chicago, IL). The study was approved by the Research Ethics Board of The Hospital for Sick Children, Ontario, Canada (No. 1000013651).
2. Results A total of 87 patients were identified through health records. Forty patients were excluded from the study because they did not meet the inclusion criteria or declined to participate. Forty-seven patients met the inclusion criteria, and study packages containing a study invitation letter and a research consent form were sent by mail. We then attempted to contact parents or patients via telephone to follow-up. Patients who agreed to participate then came for a clinic visit, which included a detailed clinical history, physical examination, pulmonary function testing, and cardiopulmonary exercise testing. Of the 47 patients, 28 agreed to participate and were prospectively tested. Twelve patients could not be contacted, and 7 were either too busy or lived too far to come for testing (Fig. 1). Of 28 patients in the study population, 12 were male and 16 were female. The mean age at the time of lobectomy was 13 months (range, 3 days to 56 months). Nineteen patients (68%) had an antenatal diagnosis. Thirteen patients (46.4%) were asymptomatic before lobectomy. There were complications in 5 patients: 2 with persistent pneumothoraces and 3 with atelectasis. All patients underwent thoracotomy. The distribution of the types of operation was as follows: 8 right upper lobectomy, 10 right lower lobectomy, 4 left upper lobectomy, and 6 left lower lobectomy. Twenty-six patients (92%) had a CPAM, 1 patient (4%) had an intralobar sequestration, and 1 patient (4%) had chronic pneumonia confirmed on pathology. The mean follow-up age of the participants was 12.8 years (range, 8-18 years). Twenty-eight patients underwent pulmonary function testing, and 27 patients underwent cardiopulmonary exercise testing (Table 1). The mean TLC was 96% predicted, the mean FVC was 90% predicted, and the mean FEV1 was 82% predicted. Five patients (18.5%) had FVC lower than 80% predicted, and 13 patients (46.4%) had FEV1 lower than 80% predicted. There was no correlation between age at
854
Y. Naito et al.
Assessed for Eligibility n = 87 Eligible n = 47 (54%)
Not eligible n = 40 (46%) Not meeting inclusion criteria* n = 37 Declined to participate n = 3 (6%)
Not Recruited n = 19 (40%)
Recruited n = 28 (60%)
Unable to contact n = 12 (24%)
Completed Study Follow-up
Unable to come n = 7 (14%)
n = 28
Exercise Test n = 27
Pulmonary Function Test n = 28
Analyzed n = 28
Fig. 1 Flow diagram of participants. Eighty-seven patients were identified through health records. Forty patients were excluded from the study. Forty-seven patients met the inclusion criteria, and 28 agreed to participate. ⁎Surgery other than lobectomy (n = 22): partial lobectomy (n = 4), cyst resection (n = 8), wedge resection (n = 3), lung cancer (n = 1), more than 1 lobectomy (n = 3), and no surgery (n = 3). Diagnosis other than CPAM (n = 9): neurologically impaired (n = 1), died (n = 1), cystic fibrosis (n = 1), trauma (n = 2), chronic infection (n = 1), pneumocele (n = 1), congenital diaphragmatic hernia (n = 1), and Langerhans cell histiocytosis (n = 1). Age, ≥23 years (n = 6).
lobectomy and pulmonary function (TLC, P = .408; FVC, P = .319; FEV1, P = .174), and maximal work capacity (power, P = .280) and VO2max (P = .055). Patients with right-sided lobectomies had a significantly higher TLC than those with left-sided lobectomy, but there was no significant difference in exercise capacities (TLC, P = .010; FVC, P = .201; FEV1, P = .547; power, P = .513; VO2max, P = .326). There was also no significant difference in pulmonary function and cardiopulmonary exercise capacity between males and females (TLC, P = .179; FVC, P = .365; FEV1, P = .092; power, P = .974; VO2max, P = .520), and between lobectomy of upper and lower lobes (TLC, P = .738; FVC, P = .518; FEV1, P = .435; power, P = .786; VO2max, P =
Table 1 Results of pulmonary function tests and cardiopulmonary exercise tests
TLC % predicted FVC % predicted FEV1 % predicted Power % predicted VO2max % predicted
n
Mean (SD)
Range
28 28 28 27 27
96 (15) 90 (16) 82 (17) 84 (13) 84 (16)
46-114 40-117 39-121 57-106 48-111
.117). Nine patients (32.1%) reported having a history of asthma. Four patients with and 2 patients without history of asthma were currently on either bronchodilator or bronchodilator and inhaled steroids. There was no significant difference in pulmonary function and cardiopulmonary exercise capacity between those with and without asthma (TLC, P = .304; FVC, P = .217; FEV1, P = .262; power, P = .488; VO2max, P = .399). Two patients with and 3 patients without history of asthma had an FEV1/FVC ratio lower than 80%. The mean FEV1/FVC ratio of patients with history of asthma was 91%, and there was no significant difference between those with and without history of asthma (P = .990). Three patients were found to have a mild chest wall deformity upon physical examination, and there was no significant difference in pulmonary function and cardiopulmonary exercise capacity between those with and without chest wall deformity (TLC, P = .352; FVC, P = .327; FEV1, P = .113; power, P = .108; VO2max, P = .702). The results of multiple regression analyses of the major variables (right-sided lobectomy, symptomatic before lobectomy, and age at lobectomy b24 months), using abnormal pulmonary function tests and abnormal exercise function as outcomes, are shown in Table 2. Symptomatic presentation
Earlier lobectomy in children with congenital lung anomalies Table 2
855
Predictors of abnormal pulmonary functions and abnormal exercise capacity
Variables TLC b80% predicted FVC b80% predicted FEV1 b80% predicted Power b80% predicted VO2max b80% predicted
Right sided Symptomatic Lobectomy age b24 Right sided Symptomatic Lobectomy age b24 Right sided Symptomatic Lobectomy age b24 Right sided Symptomatic Lobectomy age b24 Right sided Symptomatic Lobectomy age b24
mo
mo
mo
mo
mo
n
P
Exp(B)
95.0% CI for Exp(B) Lower
Upper
18 15 24 18 15 24 18 15 24 18 15 24 18 15 24
.371 .999 .508 .982 .907 .315 .086 .156 .605 .757 .043 .270 .053 .662 .150
3.278 3.486E8 1.032 1.026 1.149 1.069 0.166 3.981 1.015 1.344 6.837 .967 6.881 1.511 0.955
0.243 0.000 0.941 0.104 0.113 0.939 0.022 0.589 0.960 0.207 1.062 0.910 0.976 0.237 0.898
44.148 . 1.131 10.119 11.709 1.217 1.285 26.883 1.073 8.706 44.016 1.027 48.530 9.632 1.017
CI indicates confidence interval.
was associated with a decrease work capacity (P = .043; 95% confidence interval, 1.062-44.016).
3. Discussion Although there is general agreement that symptomatic CPAM should be resected, the need for routine lobectomy in children with asymptomatic CPAM remains controversial. The controversy revolves around a comparison of the risks of lobectomy with the risks of observant management, which mainly consist of infection and the possibility of malignancy. Advocates of early routine lobectomy also cite concern about decreased compensatory lung growth in children who would be initially managed nonoperatively and would then require lobectomy later in childhood or during adulthood because of infection or cancer. When we prospectively tested our patients who had lobectomy, we found no correlation between age at lobectomy and pulmonary function or maximal work capacity, which is consistent with our findings in an earlier, retrospective study [20]. We did find a trend toward lower VO2max in patients who underwent lobectomy at older age (VO2max, P = .055). This suggests that early lobectomy may benefit in future exercise tolerance in these patients. There were several other interesting findings. First, there was a trend of higher pulmonary function and exercise capacities in patients who were asymptomatic at the time of lobectomy than in those with either pneumonia, shortness of breath, or ventilatory support before lobectomy (TLC, P = .064 FVC, P = .244; FEV1, P = .496; power, P = .070; VO2max, P = .066). This may be because the CPAM in these children was smaller, or because the symptomatic group
tended to be older at the time of lobectomy. Second, patients with right-sided lobectomy had a significantly higher TLC than those with left-sided lobectomy. This may be because lobectomy on the right side leaves 2 other lobes to compensate the lost volume, whereas lobectomy on the left side leaves only 1 lobe to compensate. The number of patients having a history of asthma was 32.1% in this study and was higher than the current estimated asthma prevalence, that is, 9.6% among children 18 years or younger [21]. Although results of pulmonary function and cardiopulmonary exercise testing between those with and without history of asthma were not significantly different, the relatively low mean of FEV1 (82%) in this subgroup may suggest underlying susceptibility to asthma in this group. In the current study, details regarding asthma were not collected (eg, age of onset). In addition, the incidence of asthma in our study may be overestimated because it was based on parental information, and most of these patients having normal FEV1/FVC ratio suggests that the incidence of ongoing airway obstruction is rare. Further study is needed to investigate the relationship between asthma and CPAM, and the timing of lobectomy. A limitation of our study included difficulty in recruiting all eligible patients because many of them were unable to be contacted. Although this resulted in a relatively small sample size, which did not fully represent the entire population, it is one of the largest studies in the literature looking at long-term pulmonary function in children who underwent lobectomy. Because of the difficulty contacting the older patients, many of whom had moved, the patients who agreed to participate in the study were younger than the patients who were eligible but not recruited. The present study demonstrates that most children undergoing surgery for CPAM have normal long-term lung
856 function, regardless of the timing of lobectomy. The lack of a statistically significant effect of age at lobectomy on pulmonary function and cardiopulmonary exercise testing implies that concern about compensatory lung growth is not a valid argument for advocating early routine lobectomy in children with asymptomatic CPAM. However, the trend toward diminished VO2max in patients who underwent lobectomy at older age suggests that cardiopulmonary exercise testing should be considered when investigating pulmonary function after lobectomy. In addition, the relatively high incidence of asthma symptoms and FEV1 below the population standard suggests that a high index of suspicion for asthma should be maintained during the longterm follow-up for these children.
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