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Introduction. Granulomatosis with polyangiitis (GPA), formerly known as Wegener?s granulomatosis, is characterized by necrotizing granulomatous inflammation in various tissues, including blood vessels, but primarily in the respiratory tract and kidneys. Clinical manifestations can be diverse, including inflammation of the eye and adnexa. Optic neuritis is a very rare ophthalmological manifestation of GPA, not previously described in a teenager. Case report. We presented a case of a 16-year-old girl with a rare extrapulmonary manifestation of GPA. The girl had a previous history of GPA and complained of a sudden blurred vision in the left eye. She was promptly referred to an ophthalmologist who noted a decreased visual acuity of 20/400 in the left eye. Colour vision was impaired in the spectrum of red colour. Clinical examination revealed normal anterior segment findings. On ophthalmoscopy, the left optic nerve oedema was noted. Urgent computed tomography of the left orbit showed a soft tissue mass around the optic nerve in the apex of the orbit. Magnetic resonance imaging confirmed the diagnosis of optic perineuritis. After pulse doses of methylprednisolone, the girl achieved complete resolution of vision in the left eye. Conclusion. If untreated, inflammation of the optic nerve can lead to a permanent loss of vision. Prompt diagnostic and adequate treatment of patients with GPA is needed in order to prevent vision-threatening complications and control the systemic disease.

Introduction. Tracheoesophageal fistula (TEF) as a complication of balloon dilatation (BD) of corrosive esophageal stricture is a very rare and serious condition. Life threatening aspiration pneumonia requests urgent lungs' protection, but overall treatment strategy is not clearly defined. Case report. Twenty-month-old female child accidentally ingested a household bleach. Caustic injury of esophagus was healing with development of strictures of cervical and proximal thoracic esophagus. TEF was developed during the third BD. Healing of TEF and pulmonary infection was achieved by exclusion of the esophagus (pharyngostoma and feeding gastrostomy together) with prolonged tracheobronchial intubation and toilette. Retrosternal colon interposition was performed a year later, with excellent functional results over four-year follow-up. Conclusion. Esophageal exclusion in the first stage, and pharyngoesophageal reconstruction in the second stage, is a useful therapeutic option in the treatment of TEF caused by balloon dilatation of corrosive esophageal stricture in children.

Primary ciliary dyskinesia (PCD) is a disease caused by impaired function of motile cilia. PCD mainly affects the lungs and reproductive organs. Inheritance is autosomal recessive and X-linked. PCD patients have diverse clinical manifestations, thus making the establishment of proper diagnosis challenging. The utility of next-generation sequencing (NGS) technology for diagnostic purposes allows for better understanding of the PCD genetic background. However, identification of specific disease-causing variants is difficult. The main aim of this study was to create a unique guideline that will enable the standardization of the assessment of novel genetic variants within PCD-associated genes. The designed pipeline consists of three main steps: (1) sequencing, detection, and identification of genes/variants, (2) classification of variants according to their effect, and (3) variant characterization using in silico structural and functional analysis. The pipeline was validated through the analysis of the variants detected in a well-known PCD disease-causing gene (DNAI1) and the novel candidate gene (SPAG16). The application of this pipeline resulted in identification of potential disease-causing variants, as well as validation of the variants pathogenicity, through their analysis on transcriptional, translational, and posttranslational levels. The application of this pipeline leads to the confirmation of PCD diagnosis and enables a shift from candidate to PCD disease-causing gene.

BACKGROUND: Acute myocarditis (AM) is defined as inflammation of the myocardium. The aim of our study is a comparative analysis of the differences between AM related and unrelated to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: The retrospective study included children with AM treated from January 2018 to November 2020. RESULTS: The study included 24 patients; 7 of 24 had AM related to SARS-CoV-2 and they were older than 7. They were more likely to have abdominal pain (P = 0.014), headache (P = 0.003), cutaneous rash (P = 0.003), and conjunctivitis (P = 0.003), while fulminant myocarditis was commonly registered in AM unrelated to SARS-CoV-2 (P = 0.04). A multisystem inflammatory syndrome in children associated with COVID-19 was diagnosed in six adolescents. Patients with AM related SARS-CoV-2 had lower serum cardiac troponin I (cTnI) (P = 0.012), and platelets (P < 0.001), but had a higher C-reactive protein (CRP) value (P = 0.04), and N-terminal-pro hormone BNP in comparison to patients with AM unrelated to SARS-CoV-2. The patients with AM related to SARS-CoV-2 had significant reduction of CRP (P = 0.007). Inotropic drug support was used for shorter durations in patients with AM related to SARS-CoV-2, than in others (P = 0.02). Children with AM related to SARS-CoV-2 had significant improvement of left ventricle systolic function on the third day in hospital (P = 0.001). Patients with AM unrelated to SARS-CoV-2 AM had more frequent adverse outcomes (P = 0.04; three died and four dilated cardiomyopathy). CONCLUSIONS: In contrast to patients with AM unrelated to SARS-CoV-2, patients with AM related to SARS-CoV-2 had a higher CRP value, polymorphic clinical presentation, shorter durations of inotropic drugs use as well as prompt recovery of left ventricle systolic function.

Background . In CLEAR-108—a phase 3, randomised, open-label study—once-daily amikacin liposome inhalation suspension (ALIS) was noninferior to twice-daily tobramycin inhalation solution (TIS) in improving lung function in patients with cystic fibrosis (CF) and chronic Pseudomonas aeruginosa infection after 3 treatment cycles (28 days on/28 days off). The CLEAR-110 extension study (ClinicalTrials.gov: NCT01316276; EudraCT: 2011-000443-24) assessed long-term safety, tolerability, and efficacy of ALIS in eligible patients who completed CLEAR-108. Methods . Patients received once-daily ALIS 590 mg for 12 treatment cycles (96 weeks). Patients were grouped by prior treatment: the “prior-ALIS” cohort received ALIS in CLEAR-108, and the “ALIS-naive" cohort received TIS in CLEAR-108. Results . Overall, 206 patients (prior-ALIS, n=92; ALIS-naive, n=114) entered CLEAR-110 and received ≥1 dose of ALIS. Most patients (88.8%) experienced ≥1 treatment-emergent adverse event (TEAE) through day 672 (end of year 2). Most TEAEs (72.3%) were mild or moderate in severity. Severe TEAEs were reported in 31 patients (15.0%). Two life-threatening TEAEs (haemoptysis; intestinal obstruction) and 1 death (cardiac failure) were reported. Twenty-one patients (10.2%) discontinued treatment due to a TEAE (mostly infective pulmonary exacerbation of CF). Mean change from baseline in forced expiratory volume in 1 second percent predicted at day 672 was −3.1% (prior-ALIS, −4.0%; ALIS-naive, −2.3%). Mean change from baseline in sputum density of P. aeruginosa at day 672 was 0.02 (prior-ALIS, −0.16; ALIS-naive, 0.19) log CFU/g. Conclusions . Long-term treatment with ALIS was well tolerated with a favourable adverse event profile and demonstrated continued antibacterial activity in CF patients with chronic P. aeruginosa infection.

The novel coronavirus disease (COVID-19) may induce multisystem inflammatory syndrome in children, which may be associated with Kawasaki-like disease, and cardiac injury. In this study, we presented three male adolescents with multisystem inflammatory syndrome and myocardial injury admitted to the hospital during the peak of COVID-19 pandemic. All of the three patients had a history of fever, gastrointestinal symptoms, polymorph rash, non-exudative conjunctivitis, and signs of acute myocarditis. One of them had renal failure. Previously, they did not have an acute infection. Upon admission, they were hypotensive and tachycardic. A nasopharyngeal swab for SARS-CoV-2 on reverse transcription-polymerase chain reaction (PCR) assay was negative, but neutralizing viral antibodies were positive. In combination with blood tests, ECG, echocardiography and computerized tomography (CT), a multisystem inflammatory syndrome associated with acute myocarditis with mild to moderate systolic dysfunction and dilated coronary arteries were diagnosed. Two of three patients had shock syndrome and required inotropic support. All patients were treated with intravenous immunoglobulins. The second patient had a fever up to 102.2°F (39°C) three days after intravenous immunoglobulins. Further, he was treated according to protocols for refractory Kawasaki disease, with an intravenous methylprednisolone pulse therapy and aspirin. After a few hours, he became afebrile and the clinical signs disappeared. The favorable short-term outcome may reflect the early recognition and adequate therapy; however, the long-term outcomes are currently unknown.

Background/Aim. Pulmonary exacerbations have negative impact on clinical course of cystic fibrosis (CF) lung disease being associated with a steeper decline in the lung function, unfavorable prognosis and impaired quality of life. The aim of this study was to determine whether an increased number of exacerbations had influence on the lung function in the patients with CF, as well as to estimate the nutritional status, gender, presence of comorbid conditions and bacterial colonization of airways as predictive factors for pulmonary exacerbations. Methods. This retrospective cohort study included 83 pediatric and adult patients, treated from 2011? 2015 in the Mother and Child Health Institute of Serbia ?Dr Vukan Cupic?. The best result of forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) in each year of follow-up was taken into account to calculate the five-year trend values of these indicators. The number of exacerbations per year of follow-up and its impact on the FEV1 decline was evaluated. Results. Mean annual decline of FEV1 and FVC were 2.4% and 1.7% respectively. The malnourished patients had the lower initial values of FEV1 and FVC, and more frequent exacerbations in comparison with the normal weight and overweight patients. The frequency of exacerbations was significantly higher in the patients chronically colonized with Burkholderia cepacia (p = 0.023). The increased number of exacerbation was proved to be the most important factor in a prediction of FEV1 decline over time (p = 0.013). Conclusion. Pulmonary exacerbations lead to the more progressive lung function decline in the patients with CF. Malnourishment and chronic airway colonization with Burkholderia cepacia result in more frequent pulmonary exacerbations.

The most frequent chronic respiratory problems in childhood are asthma and cystic fibrosis (CF). The purpose of this paper is to review basic knowledge and recent advances in oral health and associated dental morbidities in children with asthma and CF. This review considered clinical trials and systematic reviews related to oral health in children with CRD. An online base Medline was searched to determine relevant papers, using the combination of the following terms: 'asthma', 'cystic fibrosis', 'caries', 'dental erosion', and 'oral health'. Oral health problems in children with chronic respiratory diseases (CRD) may be influenced by natural course of the disease, pharmacotherapy (inhalation therapy with bronchodilators and inhaled corticosteroids in asthmatic patients, systemic antibiotics and pancreatic enzyme replacement therapy in CF patients), medication administration technique and nutritional habits. Children with CRD may have higher prevalence of oral diseases. Patients and their parents, but also general paediatricians and pulmonologists, should be aware of importance of good oral health. Dental practitioners should be more informed about risk factors and specificities of oral health in these patients. Preventive measures, early diagnosis and effective treatment strategies in children with CRD can reduce occurrence of oral diseases and improve patient's quality of life.

Summary Candida bloodstream infections (BSI) are a significant cause of mortality in intensive care units (ICU), hereof the prospective 12-months (2014-2015) hospital- and laboratory-based survey was performed at the Serbian National Reference Medical Mycology Laboratory (NRMML). Candida identification was done by a matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry and a susceptibility test, according to the Clinical and Laboratory Standards Institute methodology. Among nine centres (265 beds; 10 820 patient admissions), four neonatal/paediatric (NICU/PICUs) and five adult centres (ICUs) participated, representing 89 beds and 3446 patient admissions, 166 beds and 7347 patient admissions respectively. The NRMML received 43 isolates, 17 from NICU/PICUs and 26 from adult ICUs. C. albicans dominated highly in NICU/PICUs (~71%), whereas C. albicans and C. parapsilosis were equally distributed within adults (46%, each), both accounting for ~90% of received isolates. The resistance to itraconazole and flucytosine were 25% and 2.4% respectively. In addition, the 2 C. albicans were azole cross-resistant (4.6%). The overall incidence of CandidaBSI was ~3.97 cases/1000 patient admissions (4.93 in NICU/PICU and 3.53 in adult ICU). The 30-day mortality was ~37%, most associated with C. tropicalis and C. glabrataBSI. Data from this national survey may contribute to improving the Balkan and Mediterranean region epidemiology of CandidaBSI within ICUs.

Background: Mechanical ventilation impairs oxygenation and increases intrapulmonary shunt. Positive end-expiratory pressure (PEEP) slows derecruitment, improves lung function but can compromise hemodynamics. Objectives: To asses slow PEEP titration effect on intrapulmonary shunt, oxygenation and hemodynamics in preschool children on mechanical ventilation under general anesthesia. Methods: This was a single tertiary care center an open-label, randomized parallel group controlled clinical trial. Study included 70 children, 3 - 7 years, ASA I and II, under general anesthesia for non-cardiothoracic surgery. Children were randomly allocated either to receive PEEP titration 5 - 11 cmH2O 20 minutes before the end of anesthesia (intervention group) or to be ventilated until the end of anesthesia with constant positive end-expiratory pressure of 3 cmH2O (control group). Main outcome measures were changes in oxygenation index (PaO2/FiO2) and alveolar-arterial gradient (P(A-a)O2) between and within groups and changes in systolic blood pressure (SBP), mean arterial pressure (MAP) and heart rate (HR) in interventional group during PEEP trial. Results: Seventy children were recruited and analyzed. P(A-a)O2 and PaO2/FiO2 improved in interventional group comparing to control as consequence of PEEP titration (ΔPaO2/FiO2 -30.3 vs. 0.52; P < 0.001; ΔP(A-a)O2 6.7 vs. -1.0; P < 0.001) and within interventional group before and after PEEP titration (PaO2/FiO2 522.0 vs. 552.3; P < 0.01; P(A-a)O2 20.1 vs. 13.3; P < 0.001). Hypotension and bradycardia were not documented. Conclusions: Slow PEEP titration up to 11 cmH2O improves oxygenation, reduces intrapulmonary shunt without causing hemodynamic instability in preschool children during general anesthesia.

The aim of the study was to compare the effects of high-intensity interval training (HIIT) and nutrition advice on cardiometabolic biomarkers, hormonal parameters, and cardiorespiratory fitness in adolescent girls with obesity. Adolescent girls with obesity (n = 44, aged 13–19 years) were randomized into a 12-week intervention as follows: (i) dietary advice and HIIT (n = 22), and (ii) dietary advice only (n = 22). The concentration of biomarkers of inflammation, biochemical and hormonal testing, oral glucose tolerance test, cardiorespiratory fitness, physical activity levels, and nutrition were assessed. After a 3-month intervention, the diet+HIIT group significantly increased insulin sensitivity index (–0.34 ± 1.52 vs. 1.05 ± 3.21; p = 0.001) and work load (0.6 ± 11.3 W vs. 14.6 ± 20.2 W; p = 0.024) and decreased glucose area under the curve (–0.29 ± 4.69 vs. −0.98 ± 4.06; p = 0.040), insulin area under the curve (−9.65 ± 117.9 vs. −98.7 ± 201.8; p = 0.003), and high-sensitivity C-reactive protein (hs-CRP) (0.12 ± 1.92 mg/L vs. −1.47 ± 3.67 mg/L; p = 0.039) in comparison with the diet group. Regarding within-group changes, both groups had significant improvements in body mass index (BMI), BMI-standard deviation score, body fat percentage, and systolic blood pressure. Positive impact on waist circumference, waist circumference/height ratio, diastolic blood pressure, hs-CRP, work load, maximal heart rate, and resting heart rate was observed only after the diet+HIIT intervention. No significant change was noted in peak oxygen uptake, lipid profile, and hormonal parameters between groups after intervention. Novelty HIIT and nutrition advice increased insulin sensitivity and decreased BMI, body fat, systolic blood pressure, and diastolic blood pressure. Nutrition advice decreased BMI, body fat, and systolic blood pressure in adolescent girls with obesity.

Respiratory symptoms at rest or during exercise may restrain the physical capabilities required for normal motor and psychosocial development in children. The most frequent cause of exercise intolerance, apart from poor physical fitness, is exercise-induced bronchoconstriction (EIB), which may occur in some healthy children and in children with asthma. It is proposed that hyperventilation during exercise is associated with drying and cooling of airways, which can trigger a proinflammatory response. Several tests are used to confirm EIB, and the exercise-challenge test is the most common. Some nonpharmacologic therapies may induce airway refractoriness; warm-up exercise can result in the attenuation of EIB in more than half of the people with EIB. Prophylactic intermittent treatment with short-acting bronchodilators is the most commonly used treatment, but the conventional pharmacologic therapy for patients with uncontrolled asthma is the regular use of inhaled corticosteroids, with or without long-acting beta-agonists and montelukast. Therapy should result in optimal control of exercise-induced symptoms during habitual physical activity and also allow participation in sports activity in athletes.

The Burkholderia cepacia complex (Bcc) organisms remain significant pathogens in patients with cystic fibrosis (CF). This study was performed to evaluate the prevalence, epidemiological characteristics, and presence of molecular markers associated with virulence and transmissibility of the Bcc strains in the National CF Centre in Belgrade, Serbia. The Bcc isolates collected during the four-year study period (2010-2013) were further examined by 16 s rRNA gene, pulsed-field gel electrophoresis of genomic DNA, multilocus sequence typing analysis, and phylogenetic analysis based on concatenated sequence of seven alleles. Fifty out of 184 patients (27.2 %) were colonized with two Bcc species, B. cenocepacia (n = 49) and B. stabilis (n = 1). Thirty-four patients (18.5 %) had chronic colonization. Typing methods revealed a high level of similarity among Bcc isolates, indicating a person-to-person transmission or acquisition from a common source. New sequence types (STs) were identified, and none of the STs with an international distribution were found. One centre-specific ST, B. cenocepacia ST856, was highly dominant and shared by 48/50 (96 %) patients colonized by Bcc. This clone was characterized by PCR positivity for both the B. cepacia epidemic strain marker and cable pilin, and showed close genetic relatedness to the epidemic strain CZ1 (ST32). These results indicate that the impact of Bcc on airway colonization in the Serbian CF population is high and virtually exclusively limited to a single clone of B. cenocepacia. The presence of a highly transmissible clone and probable patient-to-patient spread was observed.

Generalized lymphatic anomaly (GLA) is a rare congenital disorder of lymphatic development, presenting with multiple lymphatic malformations in different organs and tissues. Here, we present a case of a female neonate prenatally diagnosed with foetal hydrops and a mediastinal cystic lymphatic malformation that showed postnatal expansive and infiltrative growth into the major airways, compromising mechanical ventilation and further management of the neonate. Complications that arose during surgical treatment of mediastinal structures led to the patient’s death. Lymphatic malformations were also noted in the skin at birth. Furthermore, a skin biopsy performed immediately after birth and the autopsy revealed an extremely rare diagnosis of combined macrocystic and microcystic forms of GLA with skin involvement.

Background Shortcomings of inhaled antibiotic treatments for Pseudomonas aeruginosa infection in patients with cystic fibrosis (CF) include poor drug penetration, inactivation by sputum, poor efficiency due to protective biofilm, and short residence in the lung. Methods Eligible patients with forced expiratory volume in 1 s (FEV1) ≥25% of predicted value at screening and CF with chronic P. aeruginosa infection were randomly assigned to receive 3 treatment cycles (28 days on, 28 days off) of amikacin liposome inhalation suspension (ALIS, 590 mg QD) or tobramycin inhalation solution (TIS, 300 mg BID). The primary endpoint was noninferiority of ALIS vs TIS in change from baseline to day 168 in FEV1 (per-protocol population). Secondary endpoints included change in respiratory symptoms by Cystic Fibrosis Questionnaire-Revised (CFQ-R). Results The study was conducted February 2012 to September 2013. ALIS was noninferior to TIS (95% CI, −4.95 to 2.34) for relative change in FEV1 (L) from baseline. The mean increases in CFQ-R score from baseline on the Respiratory Symptoms scale suggested clinically meaningful improvement in both arms at the end of treatment in cycle 1 and in the ALIS arm at the end of treatment in cycles 2 and 3; however, the changes were not statistically significant between the 2 treatment arms. Treatment-emergent adverse events (TEAEs) were reported in most patients (ALIS, 84.5%; TIS, 78.8%). Serious TEAEs occurred in 17.6% and 19.9% of patients, respectively; most were hospitalisations for infective pulmonary exacerbation of CF. Conclusions Cyclical dosing of once-daily ALIS was noninferior to cyclical twice-daily TIS in improving lung function. ClinicalTrials.gov Identifier: NCT01315678

Introduction/Objective. Dysfunction of the axonemal structure leads to ciliopathies. Sensory and motile ciliopathies have been associated with numerous pediatric diseases, including respiratory diseases. Primary ciliary dyskinesia (PCD) is ciliopathy linked to the dysfunction of motile cilia. Motile ciliary dysfunction in childhood leads to chronic rhinosinusitis, persistent cough, neonatal respiratory distress, bronchiectasis, and situs inversus (SI) have 50% of patients. These symptoms are common among pediatric lung diseases, which additionally makes it difficult to establish the accurate diagnosis. The aim of the study was to point out the significance of genomic profiling for patients with suspected ciliopathies and to design a strategy for genomic analysis relevant for differential diagnosis of lung disease patients with suspected ciliopathies. Methods. We conducted a bioinformatic analysis of data generated by New Generation Sequencing (NGS) approach of 21 patients with final or suspected diagnosis of PCD. It was analyzed 93 genes: 29 PCD genes, 45 genes related to individual symptoms of lung diseases, and 19 genes related to sensory ciliopathies. Results. The algorithm we have designed, enabled us to establish the clinical and genetic diagnosis for 17/21 (80.95%) patients, among which 11/21 (52.38%) were PCD patients. In 3/21 (14.28%) patients we detected monoallelic variants in PCD disease-causing genes. In 6/21 (28.57%) patients, variants in genes for other pulmonary diseases were detected, and for one patient, genetic background of disease remained unclear. Conclusion. An improved strategy for easier and faster establishment of final diagnosis of ciliopathies is mandatory and includes both, clinical and genetic confirmation of disease. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. III41004]

Allergic bronchopulmonary aspergillosis/ABPA and allergic fungal rhinosinusitis/AFRS are pulmonary disorders caused by allergic reactions against antigens of Aspergillus sp., usually in patients with asthma, cystic fibroses/CF and nasal polyposis/NP. The aim of the present study was to clarify if ABPA and AFRS could be considered as united airway infections. The prospective study included 75 ABPA patients divided into two groups: I) with CT confirmation of rhinosinusitis and positive fungal finding in sinuses (ABPA+AFRS group) and II) without CT or mycological AFRS confirmation (ABPA group). Out of 75 patients with ABPA, 68% had asthma, 17.3% had CF and 14.6% had asthma and bronchiectasis. In 43/75 (57.3%) ABPA patients CT of paranasal sinuses revealed mucosal thickening with hyperdense lesions (ABPA+AFRS group). Nasal symptoms preceded chest symptoms in 28/75 (37.3%) patients, vice versa in 17/75 (22.7%) and occurred simultaneously in 21/75 (28%) patients. All patients had positive SPT on A. fumigatus, 13 had positive SPT on both, A. fumigatus and Alternaria alternate and 11 had positive SPT on both, A. fumigatus and Penicillium sp. Allergic mucin was seen in all ABPA+AFRS patients and fungal hyphae in 26/43 (60.4%). Culture grew Aspergillus spp. in 90% patients from ABPA+AFRS group. This is the first prospective study which analysed association of ABPA and AFRS. The pathogenesis of ABPA and AFRS share several common features, and AFRS can be considered as the upper airway counterpart of ABPA. This study is one step forward in clarifying mechanism by which airborne fungi turn from ‘normal flora’ into triggers of immunological reactions, resulting in ABPA/AFRS.

Primary ciliary dyskinesia (PCD) is a rare inherited autosomal recessive or X-linked disorder that mainly affects lungs. Dysfunction of respiratory cilia causes symptoms such as chronic rhinosinusitis, coughing, rhinitis, conductive hearing loss and recurrent lung infections with bronchiectasis. It is now well known that pathogenic genetic changes lead to ciliary dysfunction. Here we report usage of clinical-exome based NGS approach in order to reveal underlying genetic causes in cohort of 21 patient with diagnosis of PCD. By detecting 18 (12 novel) potentially pathogenic genetic variants, we established the genetic cause of 11 (9 unrelated) patients. Genetic variants were detected in six PCD disease-causing genes, as well as in SPAG16 and SPAG17 genes, that were not detected in PCD patients so far, but were related to some symptoms of PCD. The most frequently mutated gene in our cohort was DNAH5 (27.77%). Identified variants were in homozygous, compound heterozygous and trans-heterozygous state. For detailed characterization of one novel homozygous genetic variant in DNAI1 gene (c. 947_948insG, p. Thr318TyrfsTer11), RT-qPCR and Western Blot analysis were performed. Molecular diagnostic approach applied in this study enables analysis of 29 PCD disease-causing and related genes. It resulted in mutation detection rate of 50% and enabled discovery of twelve novel mutations and pointed two possible novel PCD candidate genes.

Background Laryngomalacia (LM) is the most common congenital anomaly of larynx that causes stridor in children. We evaluated the efficacy of epiglottic suture and laser epiglottopexy for treatment of infants with severe LM. Methods Surgical intervention was performed in 19 patients with severe LM, after the diagnosis was established using flexible laryngotracheobronchoscopy. Five patients had isolated type 1 LM, and 14 patients had a combination of type 1 and 3 LM. Indication for surgical treatment was the presence of LM with at least one of the following: malnutrition (body mass index [BMI] Z score 3. Results Epiglottic suture was performed in 11 patients, and laser epiglottopexy in eight, at mean age 3.95 ± 2.4 months. Rate of operation was 2.2-fold greater for more severe anomaly (combination of type 1 and 3 LM) than for isolated type 1. At 6 month follow up symptoms had gradually improved, as well as nutritional status, with increase of mean BMI Z score from –3.7 to –0.9 (P

The modified Chrispin-Norman radiography score (CNS) is used in evaluation of radiographic changes in children with cystic fibrosis (CF). We evaluated the correlation of modified CNS with peak exercise capacity (Wpeak) and ventilatory efficiency (reflected by breathing reserve index—BRI) during progressive cardiopulmonary exercise testing (CPET). Thirty-six children aged 8–17 years were stratified according to their CNS into 3 groups: mild (15). CPET was performed on a cycle ergometer. Lung function tests included spirometry and whole-body plethysmography. Patients with higher CNS had lower FEV1 (p < .001), Wpeak predicted (%; p = .01) and lower mean peak oxygen consumption (VO2peak/kg; p = .014). The BRI at the anaerobic threshold and at Wpeak was elevated in patients with the highest CNS values (p < .001). The modified CNS correlates moderately with Wpeak (R = −0.443; p = .007) and BRI (R = −0.419; p = .011). Stepwise multiple linear regression showed that RV/TLC was the best predictor of Wpeak/pred (%; B = −0.165; b = −0.494; R2 = .244; p = .002). Children with CF who have high modified CNS exhibit decreased exercise tolerance and ventilatory inefficacy during progressive effort.

Severe combined immunodeficiency (SCID), including the ‘variant’ Omenn syndrome (OS), represent a heterogeneous group of monogenic disorders characterized by defect in differentiation of T- and/or B lymphocytes and susceptibility to infections since birth. In the period of 25 years, between January 1986 and December 2010, a total of 21 patients (15 SCID, 6 OS) were diagnosed in Mother & Child Health Institute of Serbia, a tertiary-care teaching University hospital and a national referral center for patients affected with primary immunodeficiency (PID). The diagnoses were based on anamnestic data, clinical findings, and immunological and genetic analysis. The median age at the onset of the first infection was the 2nd month of life. Seven (33 %) patients had positive family history for SCID. Out of five male infants with T-B+NK- SCID phenotype, mutation analysis revealed interleukin-2 (common) gamma-chain receptor (IL2RG) mutations in 3 with positive X-linked family history, and Janus-kinase (JAK)-3 gene defects in the other two. Six patients had T-B-NK+ SCID phenotype and further 6 features of OS, 11 of which had recombinase-activating gene (RAG1or RAG2) and 1 Artemis gene mutations. One child with T+B+NK+ SCID phenotype as well had proven RAG mutation. One child each with T-B+NK+ SCID phenotype, CD8 lymphopenia and unknown phenotype remained without known underlying genetic defect. Of the eight patients who underwent hematopoetic stem cell transplant (HSCT) 5 survived, the other 13 died between 2 days and 12 months after diagnosis was made. Early diagnosis of SCID, before onset of severe infections, offers possibility for HSCT and cure. Education of primary-care pediatricians, in particular including awareness of the risk of using live vaccines and non-irradiated blood products, should improve prognosis of SCID in our setting.

Background We performed a pilot study of neonatal screening for cystic fibrosis (CF) in order to introduce it to the national screening program in Serbia. Methods Immunoreactive trypsinogen (IRT) concentrations were analyzed in dried blood spot samples. Patients were recalled for repeated measurements in case of high IRT levels. Persisting high IRT levels resulted in DNA testing for the 29 most common mutations in the CF transmembrane regulator (CFTR) gene (IRT/IRT/DNA method). Sweat chloride measurements and clinical assessment were further performed for newly diagnosed patients. Results Of 1000 samples, three were initially positive and were further analyzed for the presence of the most common CFTR mutations in the Serbian population. DNA analysis revealed two patients being homozygous for F508del mutation. One sample was false positive, as the genetic test proved to be negative and associated with normal sweat chloride concentration and unremarkable clinical presentation. Conclusions The results of our pilot study justified the expanding of the routine neonatal screening program in Serbia with CF. Data could be used in future in order to obtain accurate incidence of CF and carrier prevalence in our country.

Background: The results of many national surveys on pediatric home mechanical ventilation (HMV) in developed countries have been presented elsewhere, but data from developing countries with low national incomes are scarce. Methods: Twenty-nine pediatric patients, treated in the Mother and Child Institute of Serbia, who had been receiving long-term ventilatory support at home, were surveyed. The major criterion for initiating HMV was hypercapnia, diagnosed by blood gas analysis, performed in the morning, after awakening. Other criteria were either symptoms of hypoventilation during the night associated with an apnea index of >5, or apnoea–hypopnoea index of >15, or nocturnal hypoxemia, defined as an oxygen saturation rate of 5% of total sleep time. Results: The mean age at initiation of HMV was 9.3 years (range 0.5–17.8 years). Patients waited for HMV initiation either in hospital or at home; the mean period was 6.3 months (range 1–18 months). The subjects received HMV for a mean of 25.06 months (range 3–119 months). There was a significant difference in the duration of HMV for different underlying diseases (P= 0.046), and mechanical malfunction was strongly dependent on the duration of HMV (P= 0.011). Eleven patients underwent invasive HMV via a tracheostomy, and 18 others received non-invasive ventilation, via nasal and full-face masks. Conclusion: HMV is feasible in developing countries. Valuable reimbursement policies as well as an organized and functional network are essential for its implementation, as a standard of care in leading national pediatric hospitals.

Introduction. During the past decades a dramatic increase in the incidence of invasive fungal diseases, especially invasive aspergillosis has been observed. Undiagnosed and diagnosed late invasive aspergillosis is followed by lethality of up to 90%. Detection of early laboratory biomarkers (galactomannan and anti-Aspergillus antibodies) contributes to early diagnosis and is used for screening, as well as for monitoring therapy of aspergillosis. Objective. The aim was to evaluate usefulness of ?non-culture? methods (galactomannan and anti-Aspergillus antibodies IgA, IgM and IgG) for early diagnosis of aspergillosis in high-risk patients. Methods. Prospective two-year study involved 262 high-risk patients for aspergillosis. In pulmonology and haematology patients (adults and children) blood samples were tested on galactomannan and anti-Aspergillus antibodies. Results. Early laboratory biomarkers were statistically significantly higher in pulmonology patients (p=0.00033). However, in haematological patients galactomannan was a more frequently positive finding, while in pulmonology patients it was the finding of anti-Aspergillus antibodies. It is interesting that, despite the possible immunosuppression, in about 1/3 of haematological patients anti-Aspergillus antibodies were confirmed. Conclusion. Early diagnosis and treatment of aspergillosis represent both clinical and laboratory problem. Nowadays, the application of new ?non-culture? methods is of particular importance for the outcome of aspergillosis. Clinical features, laboratory findings of biomarkers and their correct interpretation significantly increase the possibility of timely implementation of appropriate therapy. In this regard, the new organization of reference laboratory for medical mycology has significantly improved the outcome of aspergillosis in high-risk patients in our country. However, further investigations, implementation of European standards and introduction of new diagnostic methods are necessary in this field.

Introduction. Pulmonary involvement has been described in all types of Gaucher disease (GD) but it is considered as relatively rare manifestation. There are reports suggesting that homozygosity for L444P mutation in GBA gene is associated with a substantial risk for developing primary pulmonary disease in GD. Case report. We reported sisters with pulmonary involvement in GD type III. Respiratory failure with fatal outcome at 3 years and 4 months of age occurred in K.K. due to pulmonary complications of GD. At the time enzyme replacement therapy (ERT) was not available in Serbia. J.K., homozygous for L444P mutation, developed asymptomatic pulmonary involvement at the age of 6 after 2.5 years of ERT. Pulmonary disease in J.K. was verified by high resolution computerized tomography, cytology of bronchoalveolar lavage fluid and histopathology of transbronchial lung biopsy. Conclusion. Primary lung disease in children homoallelic for L444P mutation in GBA gene emerges as a significant clinical manifestation of GD with unclear response to ERT.

Tobramycin inhalation solution is used to treat chronic Pseudomonas aeruginosa lung infection in cystic fibrosis patients. We evaluated the efficacy and safety of a novel, light-porous-particle, dry-powder formulation of tobramycin, which was developed to improve delivery efficiency to the airways and substantially reduce the delivery time. In this randomized, double-blind study, patients with cystic fibrosis (age 6–21 years) received tobramycin inhalation powder (112 mg tobramycin) twice daily (n = 46) or placebo (n = 49) via the T-326 Inhaler for one cycle, followed by two open-label cycles (all patients). Cycles were 28 days on, 28 days off treatment. The primary endpoint was change in FEV1 % predicted from baseline to Day 28 of Cycle 1. The study was terminated early based on positive results in the interim analysis. Tobramycin inhalation powder significantly improved FEV1 % predicted versus placebo at Day 28 (difference 13.3, 95% CI 5.31, 21.28; P = 0.0016). Similar changes in FEV1 were seen in patients switching from placebo to tobramycin inhalation powder in Cycle 2; improvements were maintained over time. Tobramycin inhalation powder also reduced sputum Pseudomonas aeruginosa density, respiratory-related hospitalization and antipseudomonal antibiotic use versus placebo. The most common adverse event was cough; the frequency of cough was higher in patients receiving placebo (26.5%) versus tobramycin inhalation powder (13.0%) in Cycle 1. Tobramycin inhalation powder was not associated with ototoxicity or nephrotoxicity. Administration time was between 4 and 6 minutes. In conclusion, tobramycin inhalation powder was effective and well tolerated in cystic fibrosis patients, and may offer an important treatment option to decrease the treatment burden of cystic fibrosis pseudomonas lung infections.

Introduction Laryngomalacia is the most frequent congenital anomaly of airways, and it may cause obstructive sleep apneas. The associated vocal cord paralysis may aggravate the symptoms of upper airway obstruction. Case report In a 14 month old boy severe laryngomalacia and bilateral vocal cord paralysis were diagnosed by flexible bronchoscopy. A sleep study showed a severe obstructive sleep apnoea (OSA). The patient was ventilated at home via the face mask with non invasive mechanical ventilation (CPAP) for a year. The level of pressure had to be set at 7cm H2O to correct desaturation with an improvement in mean SpO2. On the follow up bronchoscopic examination laryngomalatia was improved, vocal cord paralysis persisted and sleep study revealed significant improvement. Discussion In the patient with severe laryngomalatia and bilateral vocal cord paralysis with OSA conservative treatment with CPAP was used instead of a surgical intervention. Non invasive ventilation was used every night, for at least 6 hours, without adverse events. Invasive measurement of transdiaphragmatic pressure is the best way of titrating of CPAP level. This case report suggests the efficacy of noninvasive titrating of CPAP level by the hemoglobin oxygen saturation trend measurement. Conclusion In case of severe laryngomalatia and associated vocal cord paralysis, followed by OSA non invasive ventilation by nasal CPAP represents an effective and safe alternative to surgery.

Systemic artery-pulmonary vein fistula with a pulmonary left-left shunt is extremely rare. In this report, we present the case of a 3-month-old infant with enlarged right upper lobe systemic artery-pulmonary vein fistula and signs and symptoms of vascular tracheal compression and congestive heart failure. Two major aberrant arteries with separate origins came from the descending thoracic aorta and entered the right upper pulmonary lobe where they branched into many vascular channels and promptly drained into the enlarged right upper pulmonary vein. One of the two aberrant arteries was successfully coil embolized, and the other aberrant artery spontaneously closed after cardiac catheterization.

Chronic necrotizing pulmonary aspergillosis is a rare form of pulmonary aspergillosis. It is usually seen in middle-aged or elderly patients with underlying chronic lung disease or mild immunodeficiency, and has been only rarely encountered in children. Clinical presentation is variable and usually involves constitutional symptoms of several months' duration as well as respiratory symptoms. We present a previously well, immunocompetent, obese 10-year-old boy with cough and mild hemoptysis lasting for a couple of days and a round pulmonary infiltrate on chest radiograph. Further diagnostic investigations revealed the histopathological features of chronic necrotizing pulmonary aspergillosis in excised lung tissue, and Aspergillus fumigatus was isolated in lung tissue culture. This is one of the youngest described patients with this semi-invasive form of aspergillosis.

INTRODUCTION Many epidemiological and clinical studies have demonstrated an increased risk for the symptoms of respiratory disorders consistent with chronic bronchitis and asthma and alterations of pulmonary function tests in pig farmers. AIM The aim of this study was to determine basic pulmonary function values in workers in swine confinement buildings and to compare them with the same values in the control group of unexposed persons. The next aim was to examine the association between these values with duration of professional exposure, cigarette smoking, age, and sex of the examined persons. METHODS We randomly selected for examination 145 workers of both sex who had worked for at least 2 previous years in pig farms and spent at least 3 hours per day, 6 days per week in a swine confinement building. The farmers worked at 6 different farms with 12,383 pigs on average on each farms. The subject was eligible for the study if he had had no history of atopic disease nor any serious chronic disease, and no acute respiratory infection within 3 previous months. As control group we examined 156 subjects who had lived and/or worked in the same areas and had had no history of exposure to farming environment or any other known occupational air pollutants. In both groups the study comprised cigarette smokers and persons who had never smoked. Pulmonary function data were collected according to the standard protocol with a Micro Spirometer, (Micro Medical Ltd, England, UK). The registered parameters were FEV1 and FVC At least three satisfactory forced maximal expirations were performed by each subject and the best value was accepted for analyses. The results were also expressed as a percentage of predicted values and FEV1/FVCxlOO was calculated. RESULTS There were no differences in the main demographic characteristics between two examined groups (Table1). Mean duration of work in pig farming was 11.6 years (SD=8.5; range 2-40). The average values of examined pulmonary function tests are shown in table 2. The values of FEV1 and FVC in each groups were between 92% and 97% of predicted values, and FEV1/FVCx100 was not lower than 82%. There were no differences in the average values of FEV1 (p=0.574) and FEV1 % predicted (p=0.653) between pig farmers and control subjects. Pearson coefficient of correlation and Spearman nonparametric correlation test revealed a high level of correlation of FEV1 values with sex and age and no correlation of pig farming exposure with cigarette smoking as predictor variables (Table 3). The analysis by linear regression method showed that all examined predictor variables had the effect on the value of FEV1 (Table 4). After the elimination of the two least significant predictor variables it was possible to make the equation for prediction of FEV1 values. DISCUSSION In the present study there are no significant alterations in the values of the basic pulmonary function tests in pig farmers. In the majority of previous similar studies the differences in the average values of FEV1 and FVC between pig farmers and control subjects were also not found. However, in some studies the alterations in several more specific lung function parameters were registered. The decreased values of FEV1 during workshift were also found and they are probably connected to the bronchial hyper reactivity registered in many studies in pig farmers. Longer exposure to swine confinement environment caused more decline in FEV1 and FVC and accelerated mean age-related annual decline in FEV1 was observed reaching to 44 ml/yrs more than expected. The correlations between values of FEV, with pig farming exposure and cigarette smoking in this study were not found. However, the analysis by linear regression method showed that all examined predictor variables had the effect on the value of FEV1. In a few previous bronchoscopic, BAL, and sputum studies some signs of inflammation and morphological changes of the respiratory tract were observed. The absence of important alterations in the basic spirometric measures in this and the majority of the previous studies suggests that early airway injuries may not be readily apparent using spirometric measures of lung function. CONCLUSION In contrast to other world studies, our study comprised an important number of women farmers, but alterations associated to sex were not found. To asses the lung function in these pig farmers after several years may be of great importance.

We report the long-term follow-up of 12 pediatric-aged patients with chronic granulomatous disease (CGD). The mean age at the onset of infections was 5 months with a median delay in diagnosis of 2.5 years. Bacille Calmette–Guerin lymphadenitis was the most common presenting infection (6) followed by suppurative lymphadenitis (4), liver abscess (1), or Salmonella sepsis (1). Prophylaxis with cotrimoxazole was recommended to all patients. During the mean follow-up of 10 years (range, 4–23 years) pneumonitis was the most prevalent infection (91%) followed by lymphadenitis (83%), aphtous stomatitis (58%), and liver abscesses (25%). Seven (58%) patients developed chronic lung disease due to grossly delayed diagnosis (3) or poor compliance with antimicrobial prophylaxis (4). Five (41%) patients died during the second decade of life of aspergillosis (3) or chronic lung disease (2). Probability of survival into the third decade of life was estimated to be only 19%. We argue that HLA-identical bone marrow transplantation (BMT), if possible, should be attempted at early age because of significant morbidity and mortality in adolescence. BMT also should be considered in patients who suffer severe infections despite antimicrobial prophylaxis or patients with evidence of chronic lung disease. Possibility of elective BMT from unrelated donors remains to be carefully evaluated.

Introduction. Infants with cystic fibrosis may fail to thrive despite recommended caloric intake because of electrolyte disurbances caused by salt depletion resulting in hypochloremic metabolic alkalosis or pseudo-Bartter's syndrome. In most patients reported symptoms began in infancy, but it may be an initial presentation of disease in a previously healthy adolescent. Case report. A 15-year-old boy was admitted for evaluation of recurrent episodes of malaise associated with dehydration and acute renal insufficiency. Laboratory analysis showed hypochloremic metabolic alkalosis with hyponatremia and hypokalemia. On admission the boy was obese, with body weight of 95.5 kg (> P97), height 174 cm (> P75), and body mass index of 31.2 kg/m2 (> P95). Physical examination was inconclusive. Blood pressure holter monitoring proved significant systolic hypertension. Routine urinalysis, protein and electrolyte levels in urine were normal. Plasma renin and aldosteron were normal. Sweat chloride concentration was 63 mmol/L. Genetic testing confirmed the diagnosis of cystic fibrosis. Conclusion. To our knowledge, this is the first reported case of atypical presentation of cystic fibrosis in an adolescent presented with pseudo-Bartter's syndrome and signs of obesity and hypertension. We suggest that every patient with hypochloremic metabolic alkalosis should be evaluated for cystic fibrosis.

Laryngomalacia (LM) is the most common congenital anomaly of larynx that causes stridor in children. We evaluated the efficacy of epiglottic suture and laser epiglottopexy for treatment of infants with severe LM.Surgical intervention was performed in 19 patients with severe LM, after the diagnosis was established using flexible laryngotracheobronchoscopy. Five patients had isolated type 1 LM, and 14 patients had a combination of type 1 and 3 LM. Indication for surgical treatment was the presence of LM with at least one of the following: malnutrition (body mass index [BMI] Z score -2 SD), dysphagia or symptoms of gastroesophageal reflux and mean oxygen saturation (SaO2 )92% with oxygen desaturation index (ODI) 3.Epiglottic suture was performed in 11 patients, and laser epiglottopexy in eight, at mean age 3.95 ± 2.4 months. Rate of operation was 2.2-fold greater for more severe anomaly (combination of type 1 and 3 LM) than for isolated type 1. At 6 month follow up symptoms had gradually improved, as well as nutritional status, with increase of mean BMI Z score from -3.7 to -0.9 (P 0.01). Mean preoperative SaO2 was 89.4 ± 4.3% with mean ODI of 5.8. At 6 month follow up, mean SaO2 was 96.7 ± 1.1%, and mean ODI was 1.2 (P 0.01).Epiglottic suture and laser epiglottopexy are efficient surgical techniques that lead to significant improvement of symptoms, oxygenation and nutritional status in patients with LM.

Respiratorni sincicijalni virus (RSV), RNA virus grupe Pneumovirus genus, familije Paramyxoviridae, uzrokuje bolesti respiratornog trakta kod dece i odraslih . Do navrsene prve godine života 50% dece je inficirano RSV virusom i 20-40% te odojcadi razvije infekciju donjih respiratornih puteva ispoljenu kao bronhiolitis ili pneumonija. Inace, poseban rizik od komplikacija i smrtnog ishoda usled RSV infekcije postoji kod odojcadi sa hronicnom plucnom bolesti po tipu bronhopulmonalne displazije (BPD) i cisticne fibroze, kao i kod pojedinih kategorija dece sa urođenim srcanim manama . Tokom RSV sezone u 2008-2009. godini u Institutu za zdravstvenu zastitu majke i deteta Srbije „Dr Vukan Cupic“ po prvi put je u nasoj sredini sprovedena sistematska laboratorijska dijagnostika kojom je infekcija RSV potvrđena kod 91 hospitalizovanog deteta neonatalnog i odojackog uzrata. Smrtni ishod nastupio je kod dva odojceta: jednog sa BPD i drugog sa urođenom srcanom manom i Downovim sindromom. U navedenom periodu zabeležen je i jedan smrtni ishod kod bolesnika sa BPD lecenog u Institutu za neonatologiju, kod koga je takođe dokazana RSV infekcija .

In diagnosing the aspiration of the foreign body (AFB) in children most important are: medical history, clinical signs and positive radiography of the lungs. Common dilemmas in the diff erential diagnosis are life-threatening asthma attacks or difficult pneumonia. Conventional rigid bronchoscopy (RB) is not recommended as a routine method. Virtual bronchoscopy (VB) can be a diagnostic tool for solving dilemmas. Fiber-optic bronchoscopy (FOB) has a therapeutic stake in severe cases. Herein, we describe a girl, at the age of 6, who was hospitalized due to rapid bronchoconstriction and based on the anamnesis, clinical symptoms and physical fi ndings the suspicion was that she aspirated the foreign body. Due to the poor general condition and possible sequel, the idea of RB was dropped out. Multidetector computed tomography of the chest and VB was performed and AFB was not found. Due to positive epidemiological situation, virus H1N1 was excluded. FOB established that the foreign body does not exist in the airways. During bronchoscopy numerous castings are aspirated from the peripheral airways which lead to faster final recovery. With additional procedures, the diagnosis of asthma was confirmed and for girl that was the first attack. Along with inhaled corticosteroids as prevention she feels well. Virtual bronchoscopy can be successfully used as a valid diagnostic procedure in suspected foreign body in the children’s lungs, but fiber-optic bronchoscopy remains most important diagnostic and therapeutic method.

We performed a pilot study of neonatal screening for cystic fibrosis (CF) in order to introduce it to the national screening program in Serbia.Immunoreactive trypsinogen (IRT) concentrations were analyzed in dried blood spot samples. Patients were recalled for repeated measurements in case of high IRT levels. Persisting high IRT levels resulted in DNA testing for the 29 most common mutations in the CF transmembrane regulator (CFTR) gene (IRT/IRT/DNA method). Sweat chloride measurements and clinical assessment were further performed for newly diagnosed patients.Of 1000 samples, three were initially positive and were further analyzed for the presence of the most common CFTR mutations in the Serbian population. DNA analysis revealed two patients being homozygous for F508del mutation. One sample was false positive, as the genetic test proved to be negative and associated with normal sweat chloride concentration and unremarkable clinical presentation.The results of our pilot study justified the expanding of the routine neonatal screening program in Serbia with CF. Data could be used in future in order to obtain accurate incidence of CF and carrier prevalence in our country.

We evaluated the exercise capacity of children with cystic fibrosis to determine whether ventilatory limitation associated with static hyperinflation is related with decreased exercise capacity, thus predisposing these children to arterial hypoxemia during progressive exercise.Thirty-seven children, ages 8-17 years, underwent spirometry, body plethysmography, and cardiopulmonary exercise testing after arterial catheter placement. According to the ratio of residual volume to total lung capacity (RV/TLC), the subjects were categorized as either with (RV/TLC30%) or without static hyperinflation (RV/TLC30%).Children with static hyperinflation showed lower values of maximum load per kilogram (% predicted) (P = .01), which was aggravated by ventilatory limitation (FEV(1)80% of predicted, peak oxygen consumption [% predicted]85%, and breathing reserve index0.7). Subjects with ventilatory limitation had significantly lower oxygen saturation (P = .04) and hypoxemia (P = .03) than did subjects without ventilatory limitation.In children with cystic fibrosis, static hyperinflation and ventilatory limitation are associated with decrease in exercise performance, oxygen saturation, and P(aO(2)) during maximum cardiopulmonary exercise testing. All children with cystic fibrosis who exhibit static hyperinflation and ventilatory limitation may require S(aO(2)) monitoring during progressive exercise.

The results of many national surveys on pediatric home mechanical ventilation (HMV) in developed countries have been presented elsewhere, but data from developing countries with low national incomes are scarce.Twenty-nine pediatric patients, treated in the Mother and Child Institute of Serbia, who had been receiving long-term ventilatory support at home, were surveyed. The major criterion for initiating HMV was hypercapnia, diagnosed by blood gas analysis, performed in the morning, after awakening. Other criteria were either symptoms of hypoventilation during the night associated with an apnea index of5, or apnoea-hypopnoea index of15, or nocturnal hypoxemia, defined as an oxygen saturation rate of90% for5% of total sleep time.The mean age at initiation of HMV was 9.3 years (range 0.5-17.8 years). Patients waited for HMV initiation either in hospital or at home; the mean period was 6.3 months (range 1-18 months). The subjects received HMV for a mean of 25.06 months (range 3-119 months). There was a significant difference in the duration of HMV for different underlying diseases (P= 0.046), and mechanical malfunction was strongly dependent on the duration of HMV (P= 0.011). Eleven patients underwent invasive HMV via a tracheostomy, and 18 others received non-invasive ventilation, via nasal and full-face masks.HMV is feasible in developing countries. Valuable reimbursement policies as well as an organized and functional network are essential for its implementation, as a standard of care in leading national pediatric hospitals.