Chronic Lower Respiratory Infections Research Articles

Surveillance and phylogenetic analysis of a pathogenic bacterium candidate in nasal discharge from children.

"The infectious organism lurking in human airways (IOLA)" is a candidate pathogenic bacterium detected in bronchoalveolar lavage fluid specimens derived from adult patients with chronic lower respiratory tract infections. Genomic analyses of IOLA have revealed that it possesses the smallest and most AT-rich genome among human-derived bacteria. However, its biological properties remain unclear because no culture method has been established for IOLA. Here, we conducted a large-scale IOLA surveillance study of nasal discharge specimens from children in Japan and investigated the correlation between IOLA detection frequency and patient characteristics. We detected IOLA in 5.4% (103 of 1,920) of pediatric nasal discharge samples. No significant differences were observed in the frequency of detection based on the patient's background. However, with respect to age, the frequency of detection tended to be significantly high at 2-3 and 6 years old. Phylogenetic analysis revealed five phylotypes in the IOLA 16S rRNA gene sequences, and the sequences detected in adult patients with respiratory infections in a previous study belonged to one of the five phylotypes. The involvement of IOLA in the symptoms is not clear, but IOLA is detected at a relatively high frequency in pediatric nasal discharge. Many subjects with detected IOLA were not always IOLA positive, and IOLA was detected transiently. Our findings suggest that IOLA is horizontally transmitted through groups in nursery and elementary schools, and there are differences in biological characteristics among the IOLA phylotypes.IMPORTANCE"The infectious organism lurking in human airways (IOLA)" is a candidate pathogenic bacterium strongly suspected to be infectious to the respiratory tracts of humans and animals. However, a culture method for IOLA has not been established yet, and its properties remain unclear. In this study, IOLA was detected at a relatively high frequency in the nasal discharge of children, and five phylotypes of IOLA were identified. One of these phylotypes was found in the bronchoalveolar lavage fluid from adult patients, suggesting lineage-specific differences in the pathogenicity of IOLA. Moreover, it was suggested that IOLA is horizontally transmitted when children gather in groups such as nursery and elementary schools. These findings strongly indicate that IOLAs have been clinically undetected so far but are spreading among children, with one lineage being involved in respiratory diseases in adults. Examining the presence of IOLA in clinical specimens may help to understand the etiology of respiratory diseases with unknown causes.

Improving the management of chronic Pseudomonas aeruginosa infection in lower respiratory tract

Pseudomonas aeruginosa is one of the most important pathogens causing chronic lower respiratory tract infections in patients with chronic lung diseases such as cystic fibrosis, bronchiectasis and chronic obstructive pulmonary disease. The poor prognosis of these diseases has been found to be associated with chronic Pseudomonas aeruginosa infection in lower respiratory tract, which can be a consequence or a cause of the disease progression depending on different circumstances. Optimizing the management of chronic Pseudomonas aeruginosa infection is of great significance to improve the prognosis of these chronic lung diseases. Unlike the therapy of acute pneumonia due to Pseudomonas aeruginosa, the goals of the management for chronic Pseudomonas aeruginosa infection are not only to control infection, but also to reduce symptoms, prevent exacerbations, stop the disease progression and improve the quality of life. In addition to systemic anti-pseudomonas therapy during exacerbations, long-term multiple measures including anti-inflammatory therapy, immunomodulatory therapy,airway clearance techniques, mucoactive therapy, etc. should also be given to the patients with chronic lower respiratory tract infection due to Pseudomonas aeruginosa.

Reduced phagocytic activity of human alveolar macrophages infected with Mycobacterium avium complex

IntroductionCo-infection of nontuberculous mycobacteria (NTM) with other bacteria is associated with increased frequency of hospitalization and reduced quality of life. However, the clinical significance of co-infection with NTM and other bacteria remains unclear. Here, we investigated the distribution of alveolar macrophage populations, characterized their phagocytic function in bronchoalveolar lavage fluid (BALF), and assessed the bactericidal function of macrophages infected with NTM using cell lines. MethodsBALF samples were prospectively obtained from 30 patients with suspected NTM lung disease to evaluate phagocytic activities of macrophages using immunostaining. Bactericidal activities of Staphylococcus aureus (S. aureus) and Mycobacterium intracellulare (M. intracellulare)-infected or -non-infected macrophages were evaluated using macrophage cell lines. ResultsEleven patients with Mycobacterium avium complex (MAC) infection and 19 patients with chronic lower respiratory tract infections except for NTM infection (controls) were enrolled. The percentage of non-polarized (HLA-DR+, CD40−, and CD163−) macrophages in patients infected with MAC was significantly higher than that in controls; non-polarized macrophages demonstrated an impaired ability to phagocytose S. aureus. In vitro experiments revealed higher intracellular S. aureus colony-forming unit counts and proinflammatory cytokine levels in M. intracellulare-infected macrophages than in non-NTM-infected macrophages. Electron microscopy showed morphologically damaged macrophages and M. intracellulare and S. aureus growing in the same phagosome. ConclusionThe proportion of alveolar macrophages (HLA-DR+, CD40−, and CD163−) with impaired phagocytosis increased in MAC-infected individuals. M. intracellulare-infected macrophages reduced bactericidal activity in vitro. Dysfunction of alveolar macrophages may contribute to persistent infection by other bacteria, leading to MAC lung disease progression.

A Neural Network-Based Method for Respiratory Sound Analysis and Lung Disease Detection

Background: Respiratory sound analysis represents a research topic of growing interest in recent times. In fact, in this area, there is the potential to automatically infer the abnormalities in the preliminary stages of a lung dysfunction. Methods: In this paper, we propose a method to analyse respiratory sounds in an automatic way. The aim is to show the effectiveness of machine learning techniques in respiratory sound analysis. A feature vector is gathered directly from breath audio and, thus, by exploiting supervised machine learning techniques, we detect if the feature vector is related to a patient affected by a lung disease. Moreover, the proposed method is able to characterise the lung disease in asthma, bronchiectasis, bronchiolitis, chronic obstructive pulmonary disease, pneumonia, and lower or upper respiratory tract infection. Results: A retrospective experimental analysis on 126 patients with 920 recording sessions showed the effectiveness of the proposed method. Conclusion: The experimental analysis demonstrated that it is possible to detect lung disease by exploiting machine learning techniques. We considered several supervised machine learning algorithms, obtaining the most interesting performance with the neural network model, with an F-Measure of 0.983 in lung disease detection and equal to 0.923 in lung disease characterisation, increasing the state-of-the-art performance.

Primary ciliary dyskinesia in children

Primary ciliary dyskinesia is characterized by impaired mucociliary clearance and contributes to the recurrence of recurrent and chronic upper and lower respiratory tract infections. In this paper we elucidated a clinical case confirmed in the Pneumology Clinic of the Institute of Mother and Child, where he was investigated by ECG, pulmonary Rg, pulmonary CT, saccharin test. Morbid history of persistent wet cough, mucopurulent sputum, nasal voice, difficult nasal breathing. Radiography of the paranasal sinuses showed signs of pansinusitis. At pulmonary CT, there were characteristic signs of chronic broncho-pulmonary processes - varicose and sac-shaped bronchiectasis, pleuro-pulmonary adhesions, fibro-atelectatic areas in various segments. Spirometry – moderate and severe restrictive and obstructive disorders.

A nationwide study of air pollution from particulate matter and daily hospitalizations for respiratory diseases in Italy

Background/aimThe relationship between air pollution and respiratory morbidity has been widely addressed in urban and metropolitan areas but little is known about the effects in non-urban settings. Our aim was to assess the short-term effects of PM10 and PM2.5 on respiratory admissions in the whole country of Italy during 2006–2015. MethodsWe estimated daily PM concentrations at the municipality level using satellite data and spatiotemporal predictors. We collected daily counts of respiratory hospital admissions for each Italian municipality. We considered five different outcomes: all respiratory diseases, asthma, chronic obstructive pulmonary disease (COPD), lower and upper respiratory tract infections (LRTI and URTI). Meta-analysis of province-specific estimates obtained by time-series models, adjusting for temperature, humidity and other confounders, was applied to extrapolate national estimates for each outcome. At last, we tested for effect modification by sex, age, period, and urbanization score. Analyses for PM2.5 were restricted to 2013–2015 cause the goodness of fit of exposure estimation. ResultsA total of 4,154,887 respiratory admission were registered during 2006–2015, of which 29% for LRTI, 12% for COPD, 6% for URTI, and 3% for asthma. Daily mean PM10 and PM2.5 concentrations over the study period were 23.3 and 17 μg/m3, respectively. For each 10 μg/m3 increases in PM10 and PM2.5 at lag 0–5 days, we found excess risks of total respiratory diseases equal to 1.20% (95% confidence intervals, 0.92, 1.49) and 1.22% (0.76, 1.68), respectively. The effects for the specific diseases were similar, with the strongest ones for asthma and COPD. Higher effects were found in the elderly and in less urbanized areas. ConclusionsShort-term exposure to PM is harmful for the respiratory system throughout an entire country, especially in elderly patients. Strong effects can be found also in less urbanized areas.

Анализ структуры и антибиотикорезистентности этиологически значимых возбудителей хронической инфекции нижних дыхательных путей у детей с муковисцидозом, проживающих в г. Днепре

Актуальность. Хроническое инфекционное воспаление нижних дыхательных путей, которое формируется на основе генетического дефекта уже в первые годы жизни, является ключевым фактором у больных муковисцидозом (МВ) и определяет прогноз заболевания. Спектр микроорганизмов, которые идентифицируются в нижних дыхательных путях, является весьма специфическим для МВ, но существуют динамические изменения, региональные различия по фенотипам и чувствительности к антибиотикам. Цель исследования — мониторинг результатов микробиологического исследования мокроты детей г. Днепра, больных МВ, для определения особенностей местного профиля возбудителей, их чувствительности к антибиотикам и изменений спектра за период с 2008 по 2019 год. Материалы и методы. Обследованы 37 детей с МВ в возрасте от 1 до 18 лет. Всем больным МВ было проведено микробиологическое исследование мокроты с определением видовой принадлежности выделенных штаммов бактерий и чувствительности к антибиотикам. Также проанализированы 1257 результатов микробиологического исследования мокроты больных МВ — жителей Днепропетровской области за 2008–2018 годы. Результаты. Выявлено, что за последние 10 лет в структуре этиологически значимых патогенов хронической инфекции нижних дыхательных путей у детей с муковисцидозом наблюдается постепенное увеличение доли Staphylococcus aureus и Pseudomonas aeruginosa при уменьшении распространенности Haemophilus influenzae. Установлено, что большинство выделенных штаммов Staphylococcus aureus были резистентными к действию незащищенных аминопенициллинов, карбоксипенициллинов, цефалоспоринов I и II генераций. Мукоидные штаммы Pseudomonas aeruginosa характеризовались достаточно высоким уровнем антибиотикорезистентности к защищенным цефалоспоринам III и IV поколений, фторхинолонам. Выводы. За период наблюдения с 2008 по 2019 год видовой состав микробиоты дыхательных путей у детей с МВ в г. Днепре не изменился, однако существенно изменилось соотношение высеваемых микроорганизмов. Staphylococcus aureus и Pseudomonas aeruginosa остаются ведущими патогенами инфекций нижних дыхательных путей у больных МВ, однако отмечается рост резистентности указанных патогенов к современным антибактериальным препаратам. Определение уровня резистентности микроорганизмов у конкретного больного способствует адекватному подбору антибактериальных препаратов для лечения обострений хронической бронхолегочной инфекции в соответствии с разработанными протоколами лечения и препятствует селекции устойчивых штаммов микроорганизмов.

1441Indirect effects of COVID-19 in Australia during 2020

Focus of PresentationCOVID-19 is a major health threat that has led to substantial disruption to almost all parts of society worldwide. We brought together available data to assess the impact of the first 12 months of COVID-19 in Australia, examining initial data on the indirect effects of the pandemic on Australian’s health and welfare.FindingsDuring 2020, Australia recorded lower than expected total mortality, in contrast to many other countries where excess mortality (higher than expected deaths) was observed. Age-standardised death rates for influenza and pneumonia, and chronic lower respiratory infections during both waves of COVID-19 cases were lower than in previous years. The initial impacts of the epidemic in Australia appear to have increased levels of psychological distress. However, the number of deaths by suicide in NSW, Victoria and Queensland have remained at similar levels to previous years. Important health behaviours, such as physical activity and alcohol consumption, worsened for some people but improved for others. The travel restrictions appear to have caused a reduction in injuries due to falls and road traffic accidents, particularly during the first lockdown in March-April 2020.Conclusions/ImplicationsPublic health measures introduced to control the spread of COVID-19 in Australia had both positive and negative health effects. The impact of these effects will need to be monitored over time.Key messagesThe indirect effects of COVID-19 in Australia are wide-ranging and include impacts on mental health, health behaviours and deaths from other diseases.

Heiner Syndrome and Milk Hypersensitivity: An Updated Overview on the Current Evidence.

Infants affected by Heiner syndrome (HS) display chronic upper or lower respiratory tract infections, including otitis media or pneumonia. Clinically, gastrointestinal signs and symptoms, anemia, recurrent fever and failure to thrive can be also present. Chest X-rays can show patchy infiltrates miming pneumonia. Clinical manifestations usually disappear after a milk-free diet. The pathogenetic mechanism underlying HS remains unexplained, but the formation of immune complexes and the cell-mediated reaction have been proposed. Patients usually outgrow this hypersensitivity within a few years. The aim of this review is to provide an updated overview on the current evidence on HS in children, with a critical approach on the still undefined points of this interesting disease. Finally, we propose the first structured diagnostic approach for HS.

Life loss per death of respiratory disease attributable to non-optimal temperature: results from a national study in 364 Chinese locations

Many studies have linked temperature with respiratory deaths, but epidemiological evidence of temperature-attributable years of life lost (YLL) from respiratory diseases is limited. Daily respiratory YLL rates were calculated using mortality data from 364 locations of China during 2006–2017, and meteorological data were collected for the same period. First, the distributed lag non-linear model (DLNM) was applied to estimate specific temperature-respiratory YLL rate associations in each location. Then multivariable meta-analysis was conducted to pool the location-specific estimates. Finally, we calculated the average life loss per death (LLD) to quantify the respiratory mortality burden of non-optimal temperature. Subgroup analyses were conducted by gender, age, region and cause of death. Inversely J-shaped association was observed between non-optimal temperature and respiratory YLL rate in China. The minimum YLL-rate temperature was 26.9 °C nationwide. An average of 1.37 years (95% CI: 1.06–1.65) LLD was attributable to non-optimal temperatures with 2.06 years (95% CI: 1.57–2.60) for pneumonia, 2.03 years (95% CI: 1.76–2.31) for chronic lower respiratory infections (LRTI), 0.88 years (95% CI: 0.65–1.09) for chronic obstructive pulmonary disease (COPD), most of which was attributed to moderate cold (0.73 years, 95% CI: 0.65–0.80). LLD caused by non-optimal temperature was higher in males, the young, and north China. Exposure to non-optimal temperature increases respiratory YLL rate in China, most of which were attributed to moderate cold. People with respiratory diseases including pneumonia, chronic LRTI and COPD are vulnerable to non-optimal temperature exposure. The result of this study provides useful information to reduce temperature-related respiratory disease burden.

Implementation of a screening tool for primary ciliary dyskinesia (PCD) in a pediatric otolaryngology clinic

BackgroundPrimary ciliary dyskinesia (PCD) is a rare genetic disease arising from motile ciliary dysfunction and associated with recurrent and chronic upper and lower respiratory tract infections. Pediatric otolaryngologists may see these patients prior to the development of lung disease. Features of PCD may overlap with other suppurative respiratory diseases, creating diagnostic challenges. A simple screening tool would be beneficial to identify potential patients who have chronic upper respiratory tract disease requiring further specialist evaluation. ObjectiveTo test a simple screening tool consisting of four questions to detect PCD in children with chronic otitis media and chronic rhinosinusitis seen in a tertiary otolaryngology clinic. MethodsA prospective, single site, observational study in a tertiary care pediatric otolaryngology clinic. Children aged 3–17 years diagnosed with chronic otitis media or rhinosinusitis with onset at less than 2 years of age were recruited. All study subjects had at least one of four key clinical features for PCD as determined by answers to screening questions, while control subjects had none. All participants completed a medical history questionnaire and nasal nitric oxide measurements. Those with reduced nasal nitric oxide levels were referred to our PCD center for further evaluation. ResultsA total of 153 patients were screened and 62 subjects were enrolled. Of those, 35 were enrolled as study subjects and 27 as matched controls. Study subjects had mean age of 7.5 years (3.2–16.5) with pre-screening diagnosis of chronic otitis media (n = 29) or chronic rhinosinusitis (n = 6). Control subjects (n = 27) had mean age 7.2 years (3.0–16.3) with pre-screening diagnosis of chronic otitis media (n = 25), and chronic rhinosinusitis (n = 2). There were no differences in subject demographics or mean nasal nitric oxide values between the two groups (179.8 vs 210.8 nl/min). Ten individuals had low nasal nitric oxide values, 7 of which were normal on repeat testing. Three subjects failed to return for follow up evaluations. Four referrals were made for further evaluation on the basis of clinical symptoms and nasal nitric oxide results. While no new cases of PCD were detected, a subject and his sibling with recurrent sinopulmonary infections were referred for immunologic evaluation. ConclusionThe use of standardized screening questions can be used in an otolaryngology clinic to identify patients who require further evaluation for PCD or primary immunodeficiency.

The diagnostic accuracy of pre-hospital assessment of acute respiratory failure.

Introduction:Acute respiratory failure (ARF) is a common medical emergency. Pre-hospital management includes controlled oxygen therapy, supplemented by specific management options directed at the underlying disease. The aim of the current study was to characterise the accuracy of paramedic diagnostic assessment in acute respiratory failure.Methods:A nested diagnostic accuracy and agreement study comparing pre-hospital clinical impression to the final hospital discharge diagnosis was conducted as part of the ACUTE (Ambulance CPAP: Use, Treatment effect and Economics) trial. Adults with suspected ARF were recruited from the UK West Midlands Ambulance Service. The pre-hospital clinical impression of the recruiting ambulance service clinician was prospectively recorded and compared to the final hospital diagnosis at 30 days. Agreement between pre-hospital and hospital diagnostic assessments was evaluated using raw agreement and Gwets AC1 coefficient.Results:77 participants were included. Chronic obstructive pulmonary disease (32.9%) and lower respiratory tract infection (32.9%) were the most frequently suspected primary pre-hospital diagnoses for ARF, with secondary contributory conditions recorded in 36 patients (46.8%). There was moderate agreement between the primary pre-hospital and hospital diagnoses, with raw agreement of 58.5% and a Gwets AC1 coefficient of 0.56 (95% CI 0.43 to 0.69). In five cases, a non-respiratory final diagnosis was present, including: myocardial infarction, ruptured abdominal aortic aneurysm, liver failure and sepsis.Conclusions:Pre-hospital assessment of ARF is challenging, with limited accuracy compared to the final hospital diagnosis. A syndromic approach, providing general supportive care, rather than a specifically disease-orientated treatment strategy, is likely to be most appropriate for the pre-hospital environment.

Reconstitution of IgG Subclasses Following Immunoglobulin Administration in Adult Patients with Common Variable Immune Deficiency

Background: Immunoglobulin (Ig) therapy reduces the frequency and severity of infection among patients with antibody deficiency disorders. However, a subset of patients lacks adequate clinical response. Objective: The purpose of this study was to determine in adult common variable immune deficiency (CVID) patients (A) if lack of clinical response to Ig therapy correlates with lack of reconstitution of IgG subclass (es), (B) correlation between Ig dosing and/or IgG trough levels and IgG subclass reconstitution, (C) and most common impaired Streptococcus pneumoniae (S. pneumoniae) serotype antibody response. Methods: Single-institution, retrospective chart review for CVID patients at immunology clinics from 2015 to 2019. Patients were monitored every 3–6 months for IgG dosage, IgG trough levels, IgG subclass reconstitution, infectious episodes (chronic sinusitis, bronchitis, upper respiratory, and lower respiratory tract infections), urinary tract infections, and antibiotic use. Follow-up was calculated in patient years. Results: Twenty-five of 41 patients achieved complete reconstitution of all IgG subclasses, and 16/41 demonstrated intermittent or lack of reconstitution. There were significantly less (p < 0.001) infections among fully reconstituted patients (0.66 ± 0.19 infections per patient year) as compared to those with intermittent or lack of reconstitution (1.26 ± 0.13 infections per patient year). There was a significant correlation between IgG trough levels and IgG subclass reconstitution. Most common impaired S. pneumoniae serotype included 3, 4, 9n, 10a, 11a, 12f, and 15b. Conclusions: Incomplete IgG subclass reconstitution was associated with increased frequency of infections. IgG trough levels correlate with IgG subclass reconstitution. A limited number of S. pneumoniae serotype antibodies are commonly impaired in CVID.

Where We Stand: Lung Organotypic Living Systems That Emulate Human-Relevant Host-Environment/Pathogen Interactions.

Lung disorders such as chronic obstructive pulmonary disease (COPD) and lower respiratory tract infections (LRTIs) are leading causes of death in humans globally. Cigarette smoking is the principal risk factor for the development of COPD, and LRTIs are caused by inhaling respiratory pathogens. Thus, a thorough understanding of host–environment/pathogen interactions is crucial to developing effective preventive and therapeutic modalities against these disorders. While animal models of human pulmonary conditions have been widely utilized, they suffer major drawbacks due to inter-species differences, hindering clinical translation. Here we summarize recent advances in generating complex 3D culture systems that emulate the microarchitecture and pathophysiology of the human lung, and how these platforms have been implemented for studying exposure to environmental factors, airborne pathogens, and therapeutic agents.

An Insight into Bronchiectasis: Causes, Clinical Features, and Treatment Practices

Introduction: Bronchiectasis is a common, progressive respiratory disease characterized by irreversibly dilated, damaged, and thickened bronchi. It is present as a clinical syndrome of chronic cough, sputum production, and recurrent lower respiratory tract infections. The diagnosis depends on a degree of strong clinical and radiological suspicion. The aim of study was to give an overview of the causes, clinical features, and treatment practices of patients with bronchiectasis. Patients and Methods: This was a single-center, hospital-based, prospective, observational study in nonrandomized consecutive patients. All suspected cases were investigated by performing relevant blood, sputum, and radiological investigations. Diagnosis and etiology were confirmed with High Resolution Computed Tomography and clinical evaluation. Diagnosed cases were prescribed treatment as per the standard guidelines and followed up for a year. Results: Symptom wise, all enrolled patients had cough with expectoration, 71% complained of dyspnea, 41% had hemoptysis, and 35% had chest pain. Etiologically, bronchiectasis was postinfective in 46.5% and posttubercular in 34.9% cases. Antibiotics and pulmonary rehabilitation were taken by 28% of the cases, and antibiotics, pulmonary rehabilitation, and bronchodilators were taken by 25%. Conclusions: Although considered an “orphan” disease, bronchiectasis still accounts for a considerable number of patients, especially in a tertiary care center. When suspected on the chest radiograph, it can be confirmed on the high-resolution computed tomography thorax. Postinfective causes such as pneumonia and tuberculosis appear to be the predominant etiology leading to bronchiectasis. Treatment strategies are mainly symptomatic, and the disease can be controlled with appropriate antibiotics and pulmonary rehabilitation.

Сравнительная характеристика и особенности клинической картины заболевания взрослых больных муковисцидозом с хроническим инфицированием нижних дыхательных путей Pseudomonas aeruginosa и другой грамотрицательной неферментирующей флорой

Background: in Russia, the life expectancy of cystic fibrosis (CF) patients increased by 10 years in 2011–2017 being 55.49 years in 2017. However, the number of patients with the chronic infection caused by non-fermenting gram-negative bacilli (NFGNB), e.g., Burkholderia cepacia, Achromobacter spp. etc., increased as well. Aim: to evaluate the differences in the nutritional and functional status and the severity of mutations in CF patients with chronic Pseudomonas infection or NFGNB infection and to assess the sensitivity of P. aeruginosa to tobramycin in CF patients in the Northwest region of Russia. Patients and Methods: 31 patients with CF aged 18–43 years (18 men and 13 women) were examined. The duration of the study was 12 months. Spirometry, anthropometry, and sputum culture were performed. Results: P. aeruginosa alone was isolated in 18 patients (58%), Achromobacter spp. in 9 patients (29%), and Burkholderia spp. in 4 patients (13%). The patients were divided into two groups, i.e., patients with chronic Pseudomonas infection (group 1, n=18, 10 out of 18 patients with mucoid strains of P. aeruginosa) or chronic NFGNB infection (group 2, n=13). The median age and the mode age were 27 years and 27 years, respectively, in group 1 and 24 years and 22 years, respectively, in group 2. It was demonstrated that CF patients with chronic NFGNB infection are characterized by poorer nutritional status (p&lt;0.05) but similar functional status and the severity of CFTR gene mutation compared to CF patients with chronic Pseudomonas infection. It was also shown that Р. aeruginosa is highly sensitive to tobramycin (94.4%). Conclusions: in CF patients, chronic lower respiratory tract infections with Burkholderia cepacia and Achromobacter spp. account for 41.9% of gram-negative rod infections. Further studies and drug sensitivity monitoring are needed. KEYWORDS: cystic fibrosis, DNA test, chronic infection with Pseudomonas aeruginosa, Burkholderia cepacia, Achromobacter spp, non-fermenting gram-negative bacilli, CFTR mutation, nutritional status, pulmonary function tests, inhaled antibiotic therapy. FOR CITATION: Makhmutova V.R., Gembitskaya T.E., Chermenskiy A.G. et al. Comparative characteristics and clinical presentation of cystic fibrosis in adults with chronic lower respiratory tract infections with Pseudomonas aeruginosa and other non-fermenting gram-negative bacilli. Russian Medical Inquiry. 2020;4(4):186–191. DOI: 10.32364/2587-6821-2020-4-4-186-191.

Primary Immunodeficiency Disorders Among North Indian Children.

To report the distribution pattern of various categories of primary immunodeficiency disorders (PIDs) in children from North India, frequency of warning signs and critical parameters for evaluation. In this retrospective study, 528 children below 18 y of age after clinical assessment and presentation suggestive of PID were further screened by immunophenotyping for immune cell markers by flow cytometry. A total of 120 (23%) children were diagnosed with PID with median age at diagnosis being 2.5 y in males and 3.5 y in females and an average delay in diagnosis from onset of symptoms being approximately 5 y. Chronic lower respiratory tract infections, gastrointestinal symptoms like persistent diarrhea and failure to thrive were amongst the most common warning signs in these patients. PIDs were classified according to the International Union of Immunological Societies' (IUIS) criteria. The diagnosis of index study subjects included combined humoral and cellular immunodeficiency (29%), phagocytic defects (29%), followed by predominantly antibody deficiency (18%), innate immunity and dysregulation (17%) and other well-defined syndromes (7%). A family history of PID (23%), consanguineous marriage (8%) and previous sibling death (23%) were observed as major clinical predictors/clues for underlying PID. All children received prophylactic antibiotics and/or antifungals in addition to specific therapy for underlying immune deficiency. The field of PIDs in India remains largely unexplored and we are faced with various challenges in the diagnosis of PIDs due to lack of awareness as well as absence of equipped immunological laboratory support. The authors propose a methodical step-wise laboratory diagnostic approach that can facilitate early diagnosis and timely intervention of these mis/underdiagnosed disorders.

Efficacy and Safety of Stent, Valves, Vapour ablation, Coils and Sealant Therapies in Advanced Emphysema: A Meta-Analysis.

Bronchoscopic lung volume reduction (BLVR) methods have emerged as a new treatment option for patients with severe emphysema. Endobronchial valves and coils have been extensively studied. This review assesses efficacy, safety, and cost effectiveness of the BLVR procedures (stent, valves, vapor ablation, endobronchial coils, lung sealant) in patients with severe emphysema. Databases were searched until October 2016, and randomized controlled trials (RCTs) comparing available BLVR procedures to standard medical care or sham bronchoscopy were included. Random effect model and generic inverse variance approach were used for meta-analysis. Out of 381 identified records, 16 RCTs were included. As compared to recommended medical care or sham bronchoscopy, the BLVR procedures are more effective in improving quality of life [SGRQ score (WMD=-6.38; -9.12 to -3.65)] and 6MWT (WMD=24.21; 9.68-38.74) and percentage FEV1 (WMD=10.48; 7.07-13.89). Increased risk of serious adverse events (RR=2.18; 1.63-2.93), specifically for chronic pulmonary obstructive disease exacerbations and lower respiratory tract infection combined (RR=1.37; 1.07-1.75), were observed with bronchoscopic interventions, while there was no difference in number of deaths (RR=1.25; 0.79-1.99) and respiratory failure (RR=1.13; 0.57-2.21). The BLVR procedures, especially endobronchial coils, were found to be effective in the management of patients with severe emphysema irrespective of collateral ventilation. However, characterization of patients who would be most benefited from these procedures is required, and effectiveness of these procedures in long run needs to be established.

Mounier-Kuhn syndrome.

A 39-year-old man presented with a productive cough, a history of chronic dyspnea and recurrent lower respiratory tract infections. Physical examination and laboratory tests were unremarkable. A chest X-ray (A) showed an enlarged tracheal diameter (white arrows), with multiple cysts in the lower lobes (red arrows). A computed tomography scan of the chest (B) showed the dilatation of both the trachea and the two main bronchi (white arrows) with multiple diverticulae (blue arrows). It also revealed bilateral cystic bronchiectasis involving both lower lung zones (red arrows). A possibility of Mounier-Kuhn syndrome (MKS) was considered. MKS is a rare condition characterized by recurrent lower respiratory tract infections and tracheobronchial dilation that is due to atrophy of the muscular and elastic tissues in the trachea and main bronchial wall. The patient underwent bronchoscopy which demonstrated tracheal dilation with diverticulae and enlargement of both main bronchi confirming the diagnosis of MKS.

Silent enemy: Environmental tobacco smoke

Second-hand smoke, also known as environmental tobacco smoke (ETS), is one of the most harmful indoor pollutants. Exposure to ETS is a worldwide silent cause of mortality and morbidity. Although ETS had been decreased for 20 years, a lot of people who do not smoke still exposed to ETS at home, work, public places, and in vehicles. ETS is a risk factor for many important diseases such as lung cancer, chronic obstructive lung disease, asthma, cardiovascular diseases, upper and lower respiratory tract infections, and sudden infant death. In this article, the harmful effects of ETS and the effects of smoke-free environment regulation on ETS exposure were reviewed.