Comparison of clinical features of cystic fibrosis patients eligible but not on CFTR modulators to ineligible for CFTR modulators.

INTRODUCTION: Cystic fibrosis transmembrane conductance regulator (CFTR) modulator drugs target the underlying defect and improve CFTR function. They are a part of standard care in many countries, but not all patients are eligible for these drugs due to age and genotype. Here, we aimed to determine the characteristics of non-eligible patients for CFTR modulators in the CF registry of Turkey (CFRT) to highlight their clinical needs. METHODS: This retrospective cohort study included CF patient data from the CFRT in 2021. The decision of eligibility for the CFTR modulator was determined according to the 'Vertex treatment-Finder' on the Vertex® website. Demographic and clinical characteristics of patients were compared between eligible (group 1) and ineligible (group 2) groups for CFTR modulators. RESULTS: Among the study population (N = 1527), 873 (57.2%) were in group 1 and 654 (42.8%) were in group 2. There was no statistical difference between groups regarding sex, meconium ileus history, diagnoses via newborn screening, FEV1 z-score, CF-associated complications, organ transplant history, and death. Patients in group 2 had a higher incidence of pancreatic insufficiency (87.7% vs. 83.2%, p = .010), lower median height z-scores (-0.87 vs. -0.55, p < .001), lower median body mass index z-scores (-0.65 vs. -0.50, p < .001), longer days receiving antibiotics due to pulmonary exacerbation (0 [interquartile range, IQR: 0-2] vs. 0 [IQR: 0-7], p = 0.001), and more non-invasive ventilation support (2.6% vs. 0.9%, p = 0.008) than patients in group 1. CONCLUSION: The ineligible group had worse clinical outcomes than the eligible group. This highlights their need for life-changing drugs to improve clinical outcomes.

Experience of flexible bronchoscopy in the pediatric pulmonary diseases clinic.

Introduction: Flexible bronchoscopy is a valuable method in the diagnosis and treatment of respiratory tract diseases in children. This study aimed to examine the indications for and results of flexible bronchoscopy in children. Materials and Methods: The study included patients aged 0-18 years who underwent flexible bronchoscopy between 1 January 2017 and 31 December 2022. The patients were evaluated for demographic characteristics, indications for bronchoscopy, comorbidities, bronchoscopy findings, and the results of bronchoalveolar lavage. Result: During the defined study period, a total of 410 flexible bronchoscopy procedures were performed. 51.9% of the patient population were male, and 48.1% were female, with a mean age of 96.93 ± 63.45 months. The most common indication for flexible bronchoscopy was recurrent lower respiratory tract infection (26.8%), followed by chronic cough (19.1%). The bronchoalveolar lavage culture results showed that the most commonly isolated microorganisms were H. influenzae non-type b (7.8%) followed by M. catarrhalis (7.3%). Mucus obstruction and secretion (33.0%) constituted the most common bronchoscopic findings, while the flexible bronchoscopy examination was normal in 27% of patients. No serious complications occurred in any patient during or after the procedure. Conclusions: The results of this study demonstrated that the most common indication for flexible bronchoscopy was recurrent lower respiratory tract infection and the most common bronchoscopy finding was purulent secretion with mucus obstruction. Flexible bronchoscopy is an important diagnostic and treatment tool for patients with recurrent respiratory symptoms. It is a highly valuable method as it enables direct visualization of the airways and facilitates the collection of bronchoalveolar lavage samples.

Childhood interstitial lung disease in Turkey: first data from the national registry.

The childhood interstitial lung diseases (chILD) Turkey registry (chILD-TR) was established in November 2021 to increase awareness of disease, and in collaboration with the centers to improve the diagnostic and treatment standards. Here, the first results of the chILD registry system were presented. In this prospective cohort study, data were collected using a data-entry software system. The demographic characteristics, clinical, laboratory, radiologic findings, diagnoses, and treatment characteristics of the patients were evaluated. Clinical characteristics were compared between two main chILD groups ((A) diffuse parenchymal lung diseases (DPLD) disorders manifesting primarily in infancy [group1] and (B) DPLD disorders occurring at all ages [group 2]). There were 416 patients registered from 19 centers. Forty-six patients were excluded due to missing information. The median age of diagnosis of the patients was 6.05 (1.3-11.6) years. Across the study population (n = 370), 81 (21.8%) were in group 1, and 289 (78.1%) were in group 2. The median weight z-score was significantly lower in group 1 (- 2.0 [- 3.36 to - 0.81]) than in group 2 (- 0.80 [- 1.7 to 0.20]) (p < 0.001). When we compared the groups according to chest CT findings, ground-glass opacities were significantly more common in group 1, and nodular opacities, bronchiectasis, mosaic perfusion, and mediastinal lymphadenopathy were significantly more common in group 2. Out of the overall study population, 67.8% were undergoing some form of treatment. The use of oral steroids was significantly higher in group 2 than in group 1 (40.6% vs. 23.3%, respectively; p = 0.040).   Conclusion: This study showed that national registry allowed to obtain information about the frequency, types, and treatment methods of chILD in Turkey and helped to see the difficulties in the diagnosis and management of these patients. What is Known: • Childhood interstitial lung diseases comprise many diverse entities which are challenging to diagnose and manage. What is New: • This study showed that national registry allowed to obtain information about the frequency, types and treatment methods of chILD in Turkey and helped to see the difficulties in the diagnosis and management of these patients. Also, our findings reveal that nutrition should be considered in all patients with chILD, especially in A-DPLD disorders manifesting primarily in infancy.

Patients with cystic fibrosis who could not receive the CFTR modulator treatment: What did they lose in 1 year?

BACKGROUND: Cystic fibrosis (CF) is an autosomal recessive disorder caused by CF transmembrane conductance regulator (CFTR) genetic variants. CFTR modulators improve pulmonary function and reduce respiratory infections in CF. This study investigated the clinical and laboratory follow-up parameters over 1 year in patients with CF who could not receive this treatment. METHODS: This retrospective cohort study included 2018 and 2019 CF patient data from the CF registry of Turkey. Demographic and clinical characteristics of 294 patients were assessed, who had modulator treatment indications in 2018 but could not reach the treatment. RESULTS: In 2019, patients younger than 18 years had significantly lower BMI z-scores than in 2018. During the 1-year follow-up, forced expiratory volumes (FEV1) and FEV1 z-scores a trend toward a decrease. In 2019, chronic Staphylococcus aureus colonization, inhaled antipseudomonal antibiotic use for more than 3 months, oral nutritional supplement requirements, and oxygen support need increased. CONCLUSIONS: Patients who had indications for modulator treatments but were unable to obtain them worsened even after a year of follow-up. This study emphasized the importance of using modulator treatments for patients with CF in our country, as well as in many countries worldwide.

Clinical characteristics of patients requiring lung transplantation referral in national cystic fibrosis registry data.

BACKGROUND: We aimed to determine the number of cystic fibrosis (CF) patients recorded in the Cystic Fibrosis Registry of Türkiye (CFRT) who were in need of lung transplantation (LT) referral and examine clinical differences between patients who were LT candidates due to rapid forced expiratory volume in one second (FEV1) decline and LT candidates without rapid FEV1 decline in the last year to identify a preventable cause in patients with such rapid FEV1 decline. METHODS: All CF patients recorded in the CFRT in 2018 were evaluated in terms of LT. Patients were divided into those with FEV1 below 50% and in need of LT due to a decrease of 20% or more in the previous year (Group 1) and those who did not have FEV1 decline of more than 20% in the previous year but had other indications for LT (Group 2). Demographic and clinical features were compared between the two groups. RESULTS: Of 1488 patients registered in CFRT, 58 had a need for LT. Twenty patients were included in Group 1 and others in Group 2. Our findings did not reveal any significant variations in treatment, chronic infection status, or complications between the two groups. The average weight z-score was significantly higher in Group 1. Positive correlations were detected between weight z-score and FEV1 in 2017 in Group 1 and between FEV1 values in 2017 and 2018 in Group 2. CONCLUSIONS: There appears to be a relationship between the nutritional status and weight z-scores of CF patients and pulmonary function, which may indirectly affect the need for lung transplantation referral.

Pulmonary function tests in the follow-up of children with COVID-19.

The SARS-CoV-2 virus has infected more than 235 million people since it was accepted as a pandemic in March 2020. Although a milder disease is seen in the pediatric age group, the extent of lung damage and its long-term effects are still unknown. In this study, persistent respiratory symptoms and pulmonary function tests were investigated in children with COVID-19. Fifty children with a confirmed diagnosis of COVID-19 were included in the study. Patients were evaluated for ongoing respiratory symptoms and pulmonary function tests 3 months after infection. Patients with and without persistent symptoms were compared in terms of demographic, clinical, laboratory, and radiological characteristics and also disease severity. Three months after infection, persistent respiratory symptoms were found to be present in 28% of patients; cough, chest pain and tightness, dyspnea, and exertional dyspnea were the most common symptoms. Three patients had an obstructive deficit, and one had a restrictive deficit. Four patients had impaired diffusing capacity of the lungs for carbon monoxide (DLCO). A significant decrease in FEV1/FVC and an increase in lung clearance index were found in the patients with persistent respiratory symptoms. Persistent respiratory symptoms were present in 50% of patients who had severe disease and 12.5% with non-severe disease. DLCO was also significantly lower in the severe disease group.   Conclusions: Our study suggests that the persistence of respiratory symptoms is not related to the severity of acute COVID-19 in children. The inflammatory process due to COVID-19 may continue regardless of its severity, and consequently, peripheral airways may be affected. What is Known: • As compared with adults, children with COVID-19 exhibit a milder disease course and lower mortality rates. However, due to the lack of follow-up studies on children, the long-term effects of their contracting the disease are unknown. What is New: • Although COVID-19 has been thought to have a milder course in children, respiratory system symptoms persist in approximately 30% of patients 3 months after infection. The persistent respiratory symptoms suggest that the inflammatory process due to COVID-19 may continue in some children, even if the clinical findings at admission are not severe, and that the peripheral airways may be affected accordingly.

High-flow nasal cannula oxygen in children with bronchiolitis: A randomized controlled trial.

OBJECTIVE: To determine whether high-flow nasal cannula oxygen (HFNCO) provided enhanced respiratory support in bronchiolitis than low-flow oxygen (LFO). METHODS: We conducted a prospective, randomized controlled trial in children between 1 and 24 months diagnosed with moderate-to-severe bronchiolitis requiring oxygen therapy. Participants received LFO via face mask (6-10 L/min) or HFNCO (2 L/kg/min). Primary outcomes were the time that heart rate (HR) and respiratory rate (RR) return to their normal range for age and the time that baseline clinical respiratory score (CRS) regress to a lower severity score. Secondary outcomes were changes in HR, RR, and CRS over time, length of stay (LOS), duration of oxygen requirement, treatment failure, and adverse event (AE). RESULTS: Eighty-seven children were enrolled (48 in LFO; 39 in HFNCO). The time that HR and RR baseline values reached their normal range for age was shorter in HFNCO therapy (2.0 h [1.0-4.0] vs. 12.0 h [2.0-24.0], and 4.0 h [2.0-12.0] vs. 24.0 h [4.0-48.0], respectively; p < 0.001); additionally, the improvement in CRS emerged more quickly in children treated with HFNCO (2.0 h [1.0-4.0] vs. 4.0 h [2.0-24.0]; p = 0.003). While the duration of oxygen requirement (19.0 h [4.0-30.0] vs. 29.5 h [14.0-45.7]; p = 0.009) and treatment failure (3% vs. 21%) was statistically lower in children who received HFNCO, there were no differences in LOS and AE between groups. CONCLUSION: HFNCO may provide enhanced respiratory support with a notable improvement in HR, RR, and CRS than LFO. Comprehensive studies are needed to assess the clinical efficacy of HFNCO therapy.

The success of the Cystic Fibrosis Registry of Turkey for improvement of patient care.

BACKGROUND: Cystic fibrosis (CF) registries play an essential role in improving disease outcomes of people with CF. This study aimed to evaluate the association of newly established CF registry system in Turkey on follow-up, clinical, growth, treatment, and complications of people with this disease. METHODS: Age at diagnosis, current age, sex, z-scores of weight, height and body mass index (BMI), neonatal screening results, pulmonary function tests, history of meconium ileus, medications, presence of microorganisms, and follow-up were evaluated and compared to data of people with CF represented in both 2017 and 2019 registry data. RESULTS: There were 1170 people with CF in 2017 and 1637 in 2019 CF registry. Eight hundred and fourteen people were registered in both 2017 and 2019 of whom z-scores of heights and BMI were significantly higher in 2019 (p = 0.002, p =0.039, respectively). Inhaled hypertonic saline, bronchodilator, and azithromycin usages were significantly higher in 2019 (p =0.001, p = 0.001, p = 0.003, respectively). The percent predicted of forced expiratory volume in 1 sec and forced vital capacity were similar in 2017 and 2019 (88% and 89.5%, p = 0.248 and 84.5% and 87%, p =0.332, respectively). Liver diseases and osteoporosis were significantly higher, and pseudo-Bartter syndrome (PBS) was significantly lower in 2019 (p = 0.011, p = 0.001, p = 0.001, respectively). CONCLUSIONS: The z-scores of height and BMI were higher, the use of medications that protect and improve lung functions was higher and incidence of PBS was lower in 2019. It was predicted that registry system increased the care of people with CF regarding their follow-up. The widespread use of national CF registry system across the country may be beneficial for the follow-up of people with CF.

Clinical findings of patients with cystic fibrosis according to newborn screening results.

BACKGROUND: Cystic fibrosis (CF) is a lethal recessive genetic disease caused by loss of function associated with mutations in the CF trans-membrane conductance regulator. It is highly prevalent (approximately 1 in 3,500) in Caucasians. The aim of this study was to compare demographic and clinical features, diagnostic tests, treatments, and complications of patients with CF whose newborn screening (NBS) with twice-repeated immune reactive trypsinogen testing was positive, normal, and not performed. METHODS: In this study, 359 of all 1,488 CF patients recorded in the CF Registry of Turkey in 2018, who had been born through the process of NBS, were evaluated. Demographic and clinical features were compared in patients diagnosed with positive NBS (Group 1), normal (Group 2), or without NBS (Group 3). RESULTS: In Group 1, there were 299 patients, in Group 2, there were 40 patients, and in Group 3, there were 20 patients. Among all patients, the median age at diagnosis was 0.17 years. The median age at diagnosis was higher in Groups 2 and 3 than in Group 1 (P = 0.001). Fecal elastase results were higher in Group 2 (P = 0.033). The weight z-score was lower and chronic Staphylococcus aureus infection was more common in Group 3 (P = 0.017, P = 0.004, respectively). CONCLUSIONS: Frequency of growth retardation and chronic S. aureus infection can be reduced with an early diagnosis using NBS. In the presence of clinical suspicion in patients with normal NBS, further analyses such as genetic testing should be performed, especially to prevent missing patients with severe mutations.

Asthma-like symptom or "cystic fibrosis asthma"?

INTRODUCTION: The diagnosis of asthma is still a difficult problem in cystic fibrosis. There is no consensus on how to define "CF asthma". The aim of this study was to determine the role of bronchodilator response and laboratory evidence of allergy in "CF asthma". MATERIALS AND METHODS: Patients aged ≥6 years with evaluated bronchodilator response and characteristics of atopy were included in the study. Patients diagnosed with Allergic Bronchopulmonary Aspergillosis or pulmonary exacerbation were excluded. RESULT: A total of 204 CF patients were evaluated, and 40 who met the criteria were included. Asthma had been diagnosed in ten patients. A positive bronchodilator response was present in 47.3% of the patients tested. Aeroallergen sensitization was present in 52.5% of the patients. While the frequency of recurrent/history of wheezing, family history of atopy and elevated total immunoglobulin E were similar (p> 0.05), the frequencies of inhaled medication use and coexistence of asthma were statistically higher in the group with positive allergen sensitization (p<0.05). The frequencies of positive bronchodilator response (77.7% versus 37.9%) and a family history of asthma/atopy (40% versus. 23%) were found to be similar in CF asthma and CF. There were significant increases in total IgE and allergen-specific IgE and an increase in the frequency of aeroallergen sensitization in CF asthma compared to CF (p<0.05). CONCLUSIONS: Although not routinely used in the evaluation of patients, allergen specific-IgE and skin prick test for aeroallergen sensitization may be used as an adjunctive test in patients with suspected clinical findings. The recognition of CF asthma may facilitate the development of targeted therapies.

Is viral coinfection a risk factor for severe lower respiratory tract infection? A retrospective observational study.

OBJECTIVE: To determine whether viral coinfection is a risk for severe lower respiratory tract infection (LRTI). WORKING HYPOTHESIS: Children with viral coinfection had a higher risk for admission to the intensive care unit (ICU) than those with a single virus infection. STUDY DESIGN: Retrospective, observational study for 10 years. PATIENT-SUBJECT SELECTION: Children between 1 and 60 months of age hospitalized with LRTI.

Is Impulse Oscillometry System a Useful Method for the Evaluation and Follow-Up of Patients with Cystic Fibrosis?

Background: Although the impulse oscillometry system (IOS) is a noninvasive, easily accessible, well-tolerated, and alternative test, routine use of IOS in cystic fibrosis (CF) patients is not widespread. In our unit, IOS is routinely used for the evaluation and follow-up of patients with CF. We aimed to show that IOS may be utilized as a complement for measuring pulmonary function in CF patients. Materials and Methods: Retrospective data collection and analysis of pulmonary function tests on CF patients followed at our center between January 1, 2018 and February 1, 2019. IOS and spirometry data were compared as correlated with patients' clinical exacerbation, treatment response, bronchodilator response, and trends during follow-up intervals. Results: There was a significant correlation between spirometry and IOS parameters in 70 patients. In exacerbation, Z5, R5-R10, AX, Fres, and delta R5-R20 were significantly increased and X5-X20 was significantly decreased compared with baseline in 25 patients. After treatment, IOS parameters were observed to return to baseline values. In the evaluation of bronchodilator response in 33 patients, significant changes in IOS (decrease in Z5, R5-R10, AX, Fres, and delta R5-R20, and increase in X5-X10) and in spirometry [increase in forced expiratory volume in 1 s (FEV1) and forced expiratory flow during the middle half of forced vital capacity (FEF25-75)] were found after bronchodilator. While there was no significant difference between spirometry values in follow-up visits in 31 patients, there was a significant increase in Z5% and R5%-R20%. Unlike other studies, there was a significant correlation between clinical scores and IOS. Conclusions: These results show that although IOS is not the gold standard method such as spirometry, it is an alternative method that can be used successfully in the evaluation and follow-up of CF patients. Clinical Trials.gov ID: 99166796-050.06.04.

Asthma and allergic diseases are not risk factors for hospitalization in children with coronavirus disease 2019.

BACKGROUND: Coronavirus disease 2019 (COVID-19) emerged as a pandemic toward the end of 2019, causing large numbers of people to become infected and die. OBJECTIVE: To determine whether allergic diseases are a risk factor for hospitalization in COVID-19. METHODS: We conducted a study including 107 pediatric patients after COVID-19 recovery. The International Study of Asthma and Allergies in Childhood Phase 3 questionnaires were distributed together with a detailed history of environmental factors and an allergic evaluation including skin prick tests, specific immunoglobulin E tests, and spirometry. We investigated the prevalence of allergic diseases and evaluated the factors associated with hospitalization in COVID-19. RESULTS: A total of 61 (57%) patients were hospitalized and 46 (43%) patients were followed closely in the outpatient clinic. The prevalences of allergic rhinitis, asthma, atopic dermatitis, and episodic wheezing were 10.3%, 6,5%, 4.7%, and 3.7%, respectively, within the whole study population. Although having asthma with or without allergic rhinitis, atopic dermatitis, and passive tobacco exposure were not found to be related to hospitalization because of COVID-19, having a pet at home was found to decrease the risk of hospitalization (odds ratio, 0.191; 95% confidence interval, 0.047-0.779; P = .02). Spirometry tests revealed a higher forced expiratory volume in one second to forced vital capacity ratio and a peak expiratory flow reversibility in hospitalized patients than in nonhospitalized ones (P = .02 and P = .003, respectively). CONCLUSION: Asthma and allergic diseases do not seem to be risk factors for hospitalization in children because of COVID-19, and having a pet at home can be a protective effect. Pulmonary function testing seems to be important for monitoring lung damage after COVID-19.

Prospective evaluation of vascular changes in acute respiratory infections in children with cystic fibrosis

Background/aim: Acute exacerbations and chronic inflammation are risk factors for cardiovascular disease (CVD) in cystic fibrosis (CF) patients. The aim of this study was to investigate the effects of acute exacerbation therapy on arterial stiffness in children with CF. Materials and methods: Augmentation index (Aix) and pulse wave velocity (PWV) were measured before and after treatment and 1 month after the end of treatment in patients with acute exacerbation. The relationship between hemodynamic measurements and c-reactive protein (CRP) and pulmonary function tests (PFTs) was investigated. Results: Measurements before and after treatment were evaluated in 27 patients and were repeated in 21 patients who were clinically stable 1 month following acute exacerbation. There was a significant decrease in CRP and an increase in spirometry parameters after treatment. While no significant difference was found between PWV (P = 0.33), a significant difference for Aix before (41.95 ± 12.96%) and after (30.95 ± 11.47%) treatment and before treatment and stable clinical condition (34.19 ± 14.36%) was obtained (P =0.00, and P =0.01, respectively). No significant difference in heart rate and other hemodynamic measurements was found. Pretreatment Aix is associated with poor clinical condition (PFTs, BMI, and clinical score) and systemic inflammation (CRP) (P <0.05). Conclusion: The decrease of arterial stiffness (Aix) with acute exacerbation treatment in children with CF has been demonstrated. This result shows that systemic inflammation in CF may cause an increase in arterial stiffness and recurrent exacerbations may increase the risk of CVD.

Patients eligible for modulator drugs: Data from cystic fibrosis registry of Turkey.

BACKGROUND: A better understanding of cystic fibrosis transmembrane conductance regulator biology has led to the development of modulator drugs such as ivacaftor, lumacaftor-ivacaftor, tezacaftor-ivacaftor, and elexacaftor-tezacaftor-ivacaftor. This cross-sectional study evaluated cystic fibrosis (CF) patients eligible for modulator drugs. METHODS: Data for age and genetic mutations from the Cystic Fibrosis Registry of Turkey collected in 2018 were used to find out the number of patients who are eligible for modulator therapy. RESULTS: Of registered 1488 CF patients, genetic analysis was done for 1351. The numbers and percentages of patients and names of the drugs, that the patients are eligible for, are as follows: 122 (9.03%) for ivacaftor, 156 (11.54%) for lumacaftor-ivacaftor, 163 (11.23%) for tezacaftor-ivacaftor, and 57 (4.21%) for elexacaftor-tezacaftor-ivacaftor. Among 1351 genotyped patients total of 313 (23.16%) patients are eligible for currently licensed modulator therapies (55 patients were shared by ivacaftor and tezacaftor-ivacaftor, 108 patients were shared by lumacaftor-ivacaftor and tezacaftor-ivacaftor, and 22 patients were shared by tezacaftor-ivacaftor and elexacaftor-tezacaftor-ivacaftor groups). CONCLUSIONS: The present study shows that approximately one-fourth of the registered CF patients in Turkey are eligible for modulator drugs. As, frequent mutations that CF patients have in Turkey are different from North American and European CF patients, developing modulator drugs effective for those mutations is necessary. Furthermore, as modulator drugs are very expensive currently, financial support of the government in developing countries like Turkey is noteworthy.

Evaluation of increased arterial stiffness in pediatric patients with cystic fibrosis by augmentation index and pulse wave velocity analysis.

With the increase in life expectancy, cardiovascular complications of cystic fibrosis (CF) have come to the forefront. Increased arterial stiffness is a marker of increased cardiovascular risk. The aim of this study was to compare both pulse wave velocity (PWV) and augmentation index (Aix) measurements in children with CF and to compare them with healthy controls. We hypothesized that children with CF had increased arterial stiffness, although traditional risk factors for CVD were not observed. Forty-four patients and age and sex-matched 30 healthy controls were included in the study. Hemodynamic measurements were compared in both groups, together with traditional risk factors. Peripheral blood pressure parameters of CF and control groups were similar (P > .05). Bodyweight and BMI were significantly lower in the CF group (P < .001). Serum cholesterol, HDL, and LDL levels were significantly lower in the CF group, whereas fasting blood glucose and triglyceride levels were significantly higher than the control group (P < .05). Mean ± SD Aix was significantly higher in the CF group (33.22 ± 13.87%) compared with the control group (24.93 ± 10.58%), respectively (P < .05), while PWV was similar. No significant correlation between PWV and Aix and fasting blood glucose and lipid profile in both groups (P > .05). Children with CF have been shown to have increased arterial stiffness compared to healthy children. Although there are not many traditional risk factors, increased arterial stiffness have been demonstrated in children with CF. The effects of this process starting from childhood on the development of CVD in adulthood are not known. Therefore, further studies are needed.

Risk Factors for Influenza Virus Related Severe Lower Respiratory Tract Infection in Children.

BACKGROUND: Influenza virus is one of the most common respiratory pathogens for all age groups and may cause seasonal outbreaks. Our aim was to identify risk groups and factors associated with severe clinical course including mortality in children with influenza-related lower respiratory tract infection (LRTI). METHODS: We conducted a retrospective study in children hospitalized with influenza virus LRTI from 2008 to 2018. Data on demographic features, influenza type, viral coinfection, primary and secondary bacterial infections (SBIs), time of onset of antiviral treatment, comorbidities, hospitalization length, pediatric intensive care unit admission/invasive mechanical ventilation (IMV) need and mortality were collected from medical records. RESULTS: There were 280 patients hospitalized with LRTI and median hospitalization length was 9 days. Congenital heart disease, neuromuscular disease, SBIs and late-onset antiviral treatment were independent risk factors for prolonged hospital stay (P < 0.05). Pediatric intensive care unit admission was present in 20.4% (57) of the patients and 17.1% (48) of all patients required IMV. SBIs, lymphopenia, neutrophilia, immunosuppression and human bocavirus coinfection were independent risk factors for IMV support (P < 0.05). Eighteen patients died and immunosuppression, lymphopenia and SBIs were independent risk factors for mortality (P < 0.05). CONCLUSIONS: Presence of comorbidity, SBIs, neutrophilia and lymphopenia at admission identified as risk factors for severe influenza infections including need for IMV and death. Although several studies showed that antiviral treatment reduce hospitalization, complications and mortality, there is a lack of prospective trials and patients for antiviral therapy should be carefully chosen by the clinician.

Mitochondrial depletion in CD4+ and CD19+ peripheral lymphocytes in early stage Alzheimer's disease.

Alzheimer's disease (AD) may be associated with mitochondrial defects. The aim of the present study was to investigate changes in mitochondrial abundance in peripheral lymphocytes of early and late stage AD patients. We analysed levels of mitochondrial DNA (mtDNA) and mean fluorescence intensity (MFI) of the mitochondria-specific antibody 113-1 in CD4+, CD8+, CD19+ and CD56+ peripheral lymphocytes of early and late stage AD by quantitative real-time PCR and flow cytometry, respectively. In early stage AD, the levels of mtDNA were significantly decreased in CD4+, CD19+ and CD56+ peripheral lymphocytes while the MFI of 113-1 staining was significantly decreased in CD4+ and CD19+ cells. Thus, CD4+ and CD19+ peripheral lymphocytes of early stage AD patients exhibit mitochondrial depletion, as seen both at the level of DNA and protein.