This study describes the changes in the patient characteristics and etiology of bronchiectasis in chidren from a single tertiary reference center beween 2002 and 2019. The results demonstrate that there was a major change in pulmonary function tests, distribution of etiology, sputum microbiology over the years. Baseline FEV1 values of the patients were found to be better suggesting milder form of bronchiectasis. Although post-infectious reasons seemed to be unchanged, availability of advanced diagnostic techniques made it possible to diagnose PCD in patients.
Diagnosis of bronchiectasis is often delayed in the whole world. In a study from Italy Santamaria et al reported that the median age at diagnosis was 7 years though the children were symptomatic from the median age of 6 months . In developed countries late referral to specialist or misdiagnoses are the most common reasons for diagnostic delay. In the current study median age at diagnosis was 7 years whıch was same with our previous cohort. Three different studies from Turkey and studies from indigenous populations were also reported similar diagnostic age ranges (6.2-8.5 years) [23-26]. In developing countries lack of resources and difficulty in accessing medical services are the most probable causes of the delay in diagnosis . In a recent review, Wurzel and Chang stated that better and more standardized definition of bronchiectasis in pediatric patients will facilitate earlier diagnosis, timely management and improve clinical outcomes in children with bronchiectasis .
Spirometry results of bronchectatic patients differ between the developed and developing countries. Lung functions of children from the developed countries were normal or near normal on diagnosis and stay stable longitudinally [10,29,30]. In a study conducted among 991 PCD patients from International PCD cohort comparing with reference values, mean FEV1 and mean FVC were found to be lower than the mean reference values in all age groups with best lung function in children aged 6-9 years and the worst in adults . Patients diagnosed at an early age had better lung functions and milder disease . Studies from developing countries demonstrate a negative correlation between lung function and body mass index and quality of life . Interestingly, a follow-up study enrolling Alaskan Native children confirmed patients with bronchiectasis had significantly lower FEV1/FVC ratios than the chronic suppurative pulmonary patients without bronchiectasis . In our study, baseline FEV1 values were higher compared with the previous study. Although, there was an increase in FEV1 during the follow-up in the previous study, there was no change in the current study. Early and intensive treatment of bronchiectasis has been shown to be preventing decline in FEV1 . Consistent with our study, Kapur et al reported that pulmonary functions remained stable in patients with a mean FEV1 of 76.8±20.1% of predicted after five years follow up . In the current study, better baseline pulmonary functions can be an explanation of a better treatment regimen for bronchectasis. In addition, presence of clubbing of the fingers was significantly decreased compared to the previous study supporting a milder form of bronchiectasis. Clubbing varies with a ratio of 20.7-52% and more common in developing countries [26,34,35]. In a study conducted with non-CF bronchiectatic patients, 52% had digital clubbing and patients with digital clubbing were found to have more extent bronchiectasis but there were no association with pulmonary functions . In the current study, there was no association with the clubbing of the fingers and lung functions or severity of the bronchiectasis. Although age of diagnosis did not differ, having better pulmonary functions and decreased incidence of clubbing may suggest patients in the current study had a milder form of bronchiectasis compared to 2000s. Possible explanations for these changes may be due to increased annual income, better vaccination and easy access to health care.
Besides similarity of main characteristics of bronchiectasis in developing and affluent countries, underlying etiology, nutritional status, frequency of exacerbations and severity of the disease are different . In children with bronchiectasis, an underlying disease process is identified in 63% of cases as shown in a systematic review of 12 studies including 989 children . Previous pneumonia (17%), primary immunodeficiency (16%), recurrent aspiration, including inhaled foreign body (10%), and primary ciliary dyskinesia (9%) were among the most underlying etiologies. In developed contries, immunodeficiency is more commonly observed as the underlying disease in 9-34% of patient with bronchiectasis [4,8-13,26,35,36]. On the other side, in non-affluent countries bronchiectasis consequent to previous infection are more common, causing 17% to 28% of cases [23-25,37]. An important difference between affluent and non-affluent countries in terms of etiology is PCD reported to be higher in affluent countries (15-23.8%) [10,12]. In the current study, 32.7% of patients with non-CF bronchiectasis were diagnosed as PCD which was significantly increased compared with the previous study. Bahceci et al reviewed 110 patients between 2005-2015 and compared with their previous data for etiological reasons, reporting that the frequency of asthma and tuberculosis in etiology had decreased but primary ciliary dyskinesia (26.4%) and primary immune deficiency had increased in 10 years . Underlying etiologies of non-CF bronchiectasis can be detected due to increased availability of diagnostic procedures. In our study only in 19.2% of the patients underlying etiology could not be identified similar with the studies from affluent countries [12,13]. PCD is more easily diagnosed by early recognition of signs and symptoms by physicians and availability of nasal nitric oxide, electrone microscopy, high speed videomicroscopy, immunoflorescence and genetic analysis.
Bronchiectasis has been reported to have multilobar involvement in most pediatric studies [10,12,23,25,34]. Kapur et al reported 73% children as having bilateral disease in their cohort of 52 children . In the aspect of a developing country view, multilobar disease predominates with 71% in a study from Saudi Arabia . In our study group, multilobar involvement was lower in contrast with literature. Although, there is a difference in involvement of lobes (less multilobar, more bilobar) between the previus and the current study, it did not reach statistical significance.
The British Thoracic Society bronchiectasis guideline emphasizes microbiological assessment for evaluating airway colonisation and infection . Distribution of microorganisms in pediatric bronchiectasis is similar throughout the world. Studies from affluent countries have shown that H. influenzae, S. pneumoniae and M. catarrhalis to be the major infecting lower airway organisms, whereas patients were colonized with Pseudomonas aeruginosa in 5-16% of children . In the current study, in 22.1% of the patients sputum cultures were negative, which was significantly decreased compared with the previous study. Identification of H. influenzae, S. pneumoniae and M. catarrhalis in sputum cultures were increased in this study. Increased numbers of positive sputum cultures may be due to the better qualified staff and equipment in microbiology laboratories leading to more accurate results, as the leading agents were similar in the current and the previous study. Early identification of microorganisms and effective treatment of infections may prevent progressive lung disease.
Surgery has been performed in fewer cases as the diagnosis is made promptly and the medical treatment improved. There are few data about long-term results of medical and surgical treatment, Nevertheless, correctly chosen cases may benefit from surgery. Resection of the affected lobe or segment may be another treatment option in patients with localised disease who does not respond or noncompliant to medical treatment . In our study, only seven children (6.7%) underwent lobectomy, compared to 26 of 111 children (23.4%) the previous tudy showing the changing approach in time.
This study has some limitations. It was conducted in a single reference center. As a tertiary reference centre, many patients with suspicion of PCD were referred and this approach may cause a higher proportion of PCD patients. Increased availability of the diagnostic facilities for PCD may also support this finding.
In conclusion, this longitudinal study highlights the changing underlying etiology of pediatric non-CF bronchiectasis in a developing country setting. We have demonstrated a better lung function results, higher incidence of PCD, decreased incidence of idiopathic cases. An early and etiological diagnosis is essential not only to improve the course and prognosis of disease, but also to prevent a progressive decline in lung function. By the availability of non-invasive and effective diagnostic technologies, it is more easier to diagnose underlying etiology; but still early diagnosis is a problem worldwide. Unfortunately, most of the current data reflects individual center experiences. Establishment of both national and international pediatric bronchiectasis registry is required to estimate the real prevalence, demonstrate the differences in characteristics of the disease between countries, to show the burden of the disease, and to facilitate researches and quality improvement initiatives across healthcare system.