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. There were significant differences between the pulmonary function tests at diagnosis and follow-up, underlying etiology, and rate of positive sputum microbiology between the recent and historical cohorts.
Diagnosis of bronchiectasis is often delayed worldwide [2,3]. 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 our recent cohort median age at diagnosis was 7 years which was same with our historical cohort. Three different studies from Turkey and studies from indigenous populations also reported similar age at diagnosis (6.2-8.5 years) [26-29]. In developing countries lack of resources and difficulty in accessing medical services are the most probable causes for the delay in diagnosis .
Spirometry results of bronchiectatic patients differ between the developed and developing countries. Lung functions of children from the developed countries were normal or near normal on diagnosis and stayed stable longitudinally [10,31,32]. In a study conducted among 991 PCD patients from International PCD cohort, mean FEV1 and mean FVC were 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 function and milder disease . A follow-up study enrolling Alaskan Native children showed that patients with bronchiectasis had significantly lower FEV1/FVC ratios than the chronic suppurative pulmonary patients without bronchiectasis . In our recent cohort, baseline FEV1 values were higher compared to the historical cohort. Although, there was an increase in FEV1 during the follow-up in the historical cohort, there was no change in the recent cohort. Early and intensive treatment of bronchiectasis has been shown to prevent decline in FEV1 [1,18,31]. Kapur et al. also reported that pulmonary functions remained stable in non-CF bronchiectasis patients with a mean FEV1 of 76.8±20.1% of predicted after five years follow up .
Rate of clubbing was significantly lower in the recent cohort compared to the historical cohort supporting the presence of a milder form of bronchiectasis. Rate of clubbing in non-CF bronchiectasis varies with a ratio of 20.7-52% and it is more common in developing countries [28,35,36]. In a study conducted in non-CF bronchiectatic patients, 52% had digital clubbing and patients with digital clubbing had more extensive bronchiectasis; no association with pulmonary function tests were seen . In the recent cohort, there was no association with the clubbing of the fingers and lung functions or severity of the bronchiectasis. Although the age of diagnosis did not differ, presence of better baseline pulmonary functions, decreased incidence of clubbing and decrease in follow-up exacerbation rates compared to baseline rates may suggest patients in the recent cohort had a milder form of bronchiectasis. Possible explanations for these changes may be due to increased annual incme, better vaccine coverage, earlier recognition and referral and improved access to health care.
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%) are among the most common underlying etiologies. In developed contries, immunodeficiency is more commonly observed as the underlying disease in 9-34% of patient with bronchiectasis [4,8-13,29,36,37]. In non-affluent countries bronchiectasis consequent to previous infection is more common, is the cause in 17% to 28% of cases [26-28,38]. An important difference between affluent and non-affluent countries in terms of etiology is PCD which is higher in affluent countries (15-23.8%) [10,12]. In our recent cohort, 32.7% of patients with non-CF bronchiectasis were diagnosed as PCD which was significantly higher compared to the historical cohort. Bahceci et al reviewed 110 non-CF BE patients between 2005-2015 and compared them with their previous data for underlying etiology. They reported that the frequency of asthma and tuberculosis 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 testing. In our cohort only in 19.2% of the patients underlying etiology could not be identified similar with the studies from affluent countries [12,13]. Recent developments in diagnostic testing such as nasal nitric oxide, electrone microscopy, high speed videomicroscopy, immunoflorescence and genetic analysis enabled the diagnosis of PCD much more accurately and early.
Bronchiectasis has been reported to have multilobar involvement in most pediatric studies [10,12,26,28,35]. Kapur et al reported 73% children as having bilateral disease in their cohort of 52 children . Multilobar disease predominated with a rate of 71% in a study from Saudi Arabia . In our study group, multilobar involvement was lower. Although, there was a trend in involvement of lobes (less multilobar, more bilobar) between the historical and the recent cohorts, it did not reach statistical significance.
The British Thoracic Society bronchiectasis guideline emphasizes microbiological assessment for evaluating airway colonisation and infection . Although there is limited data from developing countries, distribution of micro-organisms seems to be similar worldwide [1,17, 30,35,40]. Studies from affluent countries showed that H. influenzae, S. pneumoniae and M. catarrhalis are the major pathogens, whereas patients were colonized with Pseudomonas aeruginosa in 5-16% of children . In our recent cohort, 22.1% patients had negative sputum cultures, which was significantly lower compared to the historical cohort. Identification of H. influenzae, S. pneumoniae and M. catarrhalis in sputum cultures were increased in the recent cohort. Number of positive sputum cultures may be due to the better qualified staff and equipment in microbiology laboratories leading to more accurate laboratory identification of the microbiology results.
This study had two limitations; it was conducted in a single reference center and as a tertiary referral centre, many patients with suspicion of PCD were referred to our center which might have caused the higher proportion of PCD patients.
In conclusion, this 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 diagnosis of underlying etiology is essential not only to improve the course and prognosis of disease, but also to prevent a progressive decline in lung function. As the availability of non-invasive and effective diagnostic technologies increase, the detection rate of underlying etiology will increase and improve the outcomes of non-CF bronchiectasis.