Course Of Pulmonary Disease Research Articles

Chronic Obstructive Pulmonary Disease and Sleep Apnea Syndrome – a Multidisciplinary Problem of Clinical Medicine

Obstructive sleep apnea syndrome (OSAS) and chronic obstructive pulmonary disease (COPD) are more common pathologies in clinical practice, which are accompanied very often by cardiovascular comorbidity. The objective: to analyze the clinical features of chronic obstructive pulmonary disease course in combination with the risk of sleep apnea syndrome. Materials and methods. 47 patients with COPD III degree of bronchial obstruction, group E participated in the study: 9 (19.1%) women and 38 (80.9%) men. The study participants were divided into two groups: I group (COPD) – 32 persons, II group (COPD + apnea syndrome) – 15 individuals. Clinical, spirographic laboratory, X-ray, ultrasound, and electrocardiographic examinations were performed to the patients, the STOP-Bang questionnaire was used to determine the risk of sleep apnea syndrome development, and the influence of bronchial obstruction on the daytime sleepiness (Epworth scale) and depression (Beck questionnaire) was studied. Results. The analysis of the results of the study presented that among the examined patients with COPD 32 (68.1%) subjects were identified with a high risk of sleep apnea syndrome. In this cohort of patients there were signs of daytime sleepiness according to the Epworth scale, and according to the Beck questionnaire they scored more than 10 points, that is, a mild level of depression of situational or neurotic origin was found. It was found that among patients with COPD in combination with the risk of night apnea (II group), coronary heart disease was diagnosed in 24 (75%) cases, arterial hypertension – in 22 (68.8%) cases, diabetes – in 15 (46.9%). At the same time, the prevalence of these nosologies in patients with COPD without the risk of night apnea was significantly (p<0.05) lower. The Charlson comorbidity index in patients with COPD and risk of apnea was within 3–4 points, 10-year survival was within 77–53%. Conclusions. The high risk of apnea syndrome according to the results of the screening questionnaire, excessive daytime sleepiness, and depressive states in patients with COPD should prompt primary care physicians to refer such patients to a comprehensive polysomnography examination to confirm OSAS. After all, COPD, OSAS and cardiovascular comorbidity are characterized by a more unfavorable clinical course and prognosis than each of these diseases separately.

Багатофакторна модель прогнозування тяжкого перебігу та ураження органів і систем при Лайм-бореліозі в дітей

Lyme disease (tick-borne borreliosis, Lyme borreliosis - LB) is a multisystem zoonotic disease transmitted by the bite of infected ticks. Purpose - to develop a mathematical model for predicting the risk of severity of the course (PRSC) of LB by the risk factor for the development of disseminated LB in children who have had a tick attack. Materials and methods. To build a model for PRSC of LB using multivariate regression analysis, 121 children with LB aged 13±3 years (from 1 to 18 years) were examined, including 51 boys and 70 girls. Groups of patients: 78 children with erythema migrans, 16 - with Lyme arthritis, 27 - with nervous system lesions. The quality of the prognostic model was checked by the Neigelkerk criterion (R2), and the acceptability of the model was assessed using ANOVA analysis of variance. Serological examination of patients bitten by ticks was performed by enzyme-linked immunosorbent assay. To detect immunoglobulins of classes M (IgM) and G (IgG) to B. burgdorferi s.l. complex, test systems from Euroimmun AG (Germany) were used. IgM antibodies were determined by the test system Anti-Borrelia burgdorferi ELISA, IgG - by Anti-Borrelia plus VIsE ELIS. Blood samples with intermediate and positive results of the first stage of work were examined by immune blotting: IgM antibodies were detected using the system Anti-Borrelia EUROLINE Borrelia RN-AT (IgM), and IgG antibodies - Anti-Borrelia EUROLINE RN-AT. Results. The method of multivariate regression analysis for predicting the severe course and damage to organs and systems in children with LB, taking into account the factors and variants of the disease itself, allows to develop a mathematical model of PRSC of LB and to improve the effectiveness of treatment. Thus, all prerequisites have been created for high-quality preventive measures and reducing the risk of severe pulmonary disease. The initial data for predicting the severity of pulmonary disease were 28 factors. According to the results of the regression analysis, 24 factors were included in the model for predicting the severity of the course of pulmonary disease. Conclusions. For the first time, a multivariate regression model for PRSC of LB for pulmonary fibrosis in children was built. The weighting coefficients of each of the factors of the onset and progression of LB were taken into account: 0-10 points indicate the development of a localized stage (primary effect stage), while 11 or more points indicate a disseminated (generalized) stage. The results of the study make it possible to further develop standardized scales of the severity of LB and possible organ and system damage. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Knockdown of long noncoding RNA MIAT attenuates cigarette smoke-induced airway remodeling by downregulating miR-29c-3p–HIF3A axis

Chronic obstructive pulmonary disease (COPD) is a global public health issue and is defined as persistent airflow limitation. COPD is a major cause of morbidity and mortality worldwide. Long noncoding RNAs are involved in the course of pulmonary diseases. Here, we revealed that a long noncoding RNA called myocardial-infarction–associated transcript (MIAT) is upregulated in lung tissues of cigarette smoke (CS)-exposed mice. Knockdown of MIAT attenuated CS or CS-extract–induced inflammatory processes, epithelial-mesenchymal transition (EMT), and collagen deposition. Moreover, according to bioinformatic analyses and luciferase reporter assays, MIAT binds to microRNA-29c-3p (miR-29c-3p) and upregulates hypoxia-inducible factor 3 alpha (HIF3A), a target gene of miR-29c-3p. When the MIAT-specific short hairpin RNA and an miR-29c-3p inhibitor were cotransfected into cells, the inhibitor reversed the effects of MIAT knockdown on cell proliferation, apoptosis, inflammation, EMT, and collagen deposition. Overall, these results indicate that MIAT participates in CS-induced EMT and airway remodeling in COPD by upregulating miR-29c-3p–HIF3A axis output, thereby offering a novel promising biomarker for the assessment of COPD exacerbation induced by CS exposure.

Тяжелые респираторно-вирусные инфекции: эпигенетические механизмы предрасположенности и возможности эпигенетически-направленной терапии

The emergence of highly pathogenic strains of influenza and coronavirus (CoV) viruses has caused outbreaks of epidemics and pandemics of lung diseases, characterized by severe course and high mortality. One of the main tasks of intensive care is to stratify and minimize the risk of developing multiple organ failure (MOF) in patients during their stay in the intensive care unit (ICU). Epigenetic mechanisms of gene expression control, including DNA and RNA methylation, histone modifications and noncoding RNAs, can be used by viruses to prevent the development of innate and adaptive immunity responses, change the adequacy of the inflammatory response, and thereby contribute to the severe course of pulmonary disease. For example, Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and H5N1 influenza virus can interfere with host antigen presentation through DNA methylation and histone modifications. Presumably, the same mechanisms may be involved in patients with coronavirus disease-2019 (COVID-19), in whom tocilizumab epigenetically reduced microvascular damage. Targeting epigenetic pathways of immune modulators (e. g. tocilizumab) or repurposed drugs (e. g. statins) may provide new therapeutic options for controlling host-virus interactions during the development of critical illness. The review provides updated information on epigenetic mechanisms and repurposed drugs that affect epigenetic pathways that may be clinically effective for risk stratification and useful for the treatment of patients with severe respiratory viral infections.

Mini Review: Pulmonary Toxicity Secondary to Immunosuppressive Agents in the Treatment of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic rheumatic disease, characterized by erosive and destructive arthritis, representing an important cause of disability. Interstitial lung disease is not a rare event and can be aggravated by several immunosuppressive medications. Methotrexate, once seen as a drug associated with interstitial pneumonitis, is now seen as an agent capable of slowing or preventing the progression of lung disease related to rheumatoid arthritis. Anti-TNFs currently represent the class with the greatest impact on the course of pulmonary disease in RA, with a significant increase in mortality. Among the immunobiological agents, abatacept and Rituximab stand out in relation to the pulmonary safety profile.

Long non-coding RNA NNT-AS1 regulates proliferation, apoptosis, inflammation and airway remodeling of chronic obstructive pulmonary disease via targeting miR-582-5p/FBXO11 axis

BackgroundChronic obstructive pulmonary disease (COPD) is a kind of chronic lung disease that mainly induced by smoking-caused inflammation. Long non-coding RNAs (lncRNAs) have been reported to play a part in the course of pulmonary diseases. Here, we studied the role of lncRNA NNT-AS1 in the development of COPD. MaterialsqRT-PCR analysis and ELISA assay were applied to evaluate the expression of genes and inflammatory cytokines, respectively. CCK8 and EdU assays were utilized to assess proliferation, while flow cytometry assay was conducted to evaluate apoptosis. Luciferase reporter, RNA pull down and RIP assays were combined to explore relationships between genes. ResultsNNT-AS1 was observed to be up-regulated in cigarette smoke extract (CSE)-treated 16HBE cells. Knockdown of NNT-AS1 abolished CSE-caused suppressive effects on cell proliferation, apoptosis, inflammation and airway remodeling. Mechanistically, NNT-AS1 up-regulated FBXO11 expression via sponging miR-582-5p. Moreover, miR-582-5p inhibitor or FBXO11 overexpression counteracted NNT-AS1 silence-elicited effects on proliferation, apoptosis, inflammation and airway remodeling. ConclusionOur data revealed that NNT-AS1 played a promoting role in smoking-induced COPD via modulating miR-582-5p/FBXO11 signaling, suggesting a novel potential target for COPD treatment.

Lung disease in STAT3 hyper-IgE syndrome requires intense therapy.

Pulmonary complications are responsible for high morbidity and mortality rates in patients with the rare immunodeficiency disorder STAT3 hyper-IgE syndrome (STAT3-HIES). The aim of this study was to expand knowledge about lung disease in STAT3-HIES. The course of pulmonary disease, radiological and histopathological interrelations, therapeutic management, and the outcome of 14 STAT3-HIES patients were assessed. The patients' quality of life was compromised most by pulmonary disease. All 14 patients showed first signs of lung disease at a median onset of 1.5years of age. Lung function revealed a mixed obstructive-restrictive impairment with reduced FEV1 and FVC in 75% of the patients. The severity of lung function impairment was associated with Aspergillus fumigatus infection and prior lung surgery. Severe lung tissue damage, with reduced numbers of ATP-binding cassette sub-family A member 3 (ABCA3) positive type II pneumocytes, was observed in the histological assessment of two deceased patients. Imaging studies of all patients above 6years of age showed severe airway and parenchyma destruction. Lung surgeries frequently led to complications, including fistula formation. Long-term antifungal and antibacterial treatment proved to be beneficial, as were inhalation therapy, chest physiotherapy, and exercise. Regular immunoglobulin replacement therapy tended to stabilize lung function. Due to its severity, pulmonary disease in STAT3-HIES patients requires strict monitoring and intensive therapy.

About pulmonary disease of Fedor M. Dostoevskiy. Part 2

Clinical signs and course of pulmonary disease of Fedor M. Dostoevskiy (1821 – 1881) has been analyzed in the article on the basis of memoirs of contemporaries and physicians who followed the writer up to the end of his life. Diagnostic hypotheses of the disease and the cause of death have been discussed.

About pulmonary disease of Fedor M. Dostoevskiy. Part 1

Clinical signs and course of pulmonary disease of Fedor M. Dostoevskiy (1821 – 1881) has been analyzed in the article on the basis of memoirs of contemporaries and physicians who followed the writer up to the end of his life. Diagnostic hypotheses of the disease and the cause of death have been discussed.

RhACE2 Therapy Modifies Bleomycin-Induced Pulmonary Hypertension via Rescue of Vascular Remodeling.

Background: Pulmonary hypertension (PH) is a progressive cardiovascular disease, characterized by endothelial and smooth muscle dysfunction and vascular remodeling, followed by right heart failure. Group III PH develops secondarily to chronic lung disease such as idiopathic pulmonary fibrosis (IPF), and both hastens and predicts mortality despite of all known pharmacological interventions. Thus, there is urgent need for development of newer treatment strategies.Objective: Angiotensin converting enzyme 2 (ACE2), a member of the renin angiotensin family, is therapeutically beneficial in animal models of pulmonary vascular diseases and is currently in human clinical trials for primary PH. Although previous studies suggest that administration of ACE2 prevents PH secondary to bleomycin-induced murine IPF, it is unknown whether ACE2 can reverse or treat existing disease. Therefore, in the present study, we tested the efficacy of ACE2 in arresting the progression of group 3 PH.Methods: To establish pulmonary fibrosis, we administered 0.018 U/g bleomycin 2x/week for 4 weeks in adult FVB/N mice, and sacrificed 5 weeks following the first injection. ACE2 or vehicle was administered via osmotic pump for the final 2 weeks, beginning 3 weeks after bleomycin. Echocardiography and hemodynamic assessment was performed prior to sacrifice and tissue collection.Results: Administration of bleomycin significantly increased lung collagen expression, pulmonary vascular remodeling, and pulmonary arterial pressure, and led to mild right ventricular hypertrophy. Acute treatment with ACE2 significantly attenuated vascular remodeling and increased pulmonary SOD2 expression without measurable effects on pulmonary fibrosis. This was associated with nonsignificant positive effects on pulmonary arterial pressure and cardiac function.Conclusion: Collectively, our findings enumerate that ACE2 treatment improved pulmonary vascular muscularization following bleomycin exposure, concomitant with increased SOD2 expression. Although it may not alter the pulmonary disease course of IPF, ACE2 could be an effective therapeutic strategy for the treatment of group 3 PH.

Evaluating Pulmonary Function: An Assessment of PaO2/FIO2.

PaO2/FIO2 is used commonly for diagnosis of lung injury (acute respiratory distress syndrome and transfusion-related acute lung injury), for assessment of pulmonary disease course and therapy, and in pulmonary transplantation for evaluation of donor lungs and clinical outcome. It was developed for convenience, without formal mathematical and graphic assessment to validate its suitability for these purposes. We examined, mathematically and graphically, the relationship of PaO2/FIO2 to FIO2 at constant normal and several degrees of increased intrapulmonary shunting (QS/QT), assessing the impact of intra- and extrapulmonary factors on the relationship and thus the reliability of PaO2/FIO2. The relationship of PaO2/FIO2 varies at all shunt fractions but most with QS/QT from 0.1 to 0.3 with FIO2 approximately greater than 0.4. At higher QS/QT, the relationship is more constant and changes less with FIO2 more than 0.4. Hemoglobin concentration and arterial-venous oxygen content difference have large effects that can confound interpretation of PaO2/FIO2. Barometric pressure has a substantial effect; PCO2, base excess, and respiratory quotient have small effects. At high QS/QT with FIO2 more than 0.4, the relationship of PaO2/FIO2 to FIO2 is relatively constant. However, with QS/QT of 0.1-0.3, PaO2/FIO2 changes substantially with FIO2. Understanding the important effects of nonpulmonary factors (especially hemoglobin concentration and arterial-venous oxygen content difference) should enhance appropriate clinical use, interpretation of PaO2/FIO2, and interpretation of previous publications and future studies (especially those seeking to assess effects of anemia or transfusion on lung function). The ratio of PaO2/FIO2 is a good tool for some, but not many clinical circumstances, and is insufficiently robust for most research applications.

Differential Immune Responses and Pulmonary Pathophysiology Are Induced by Two Different Strains of Respiratory Syncytial Virus

In this study we performed comparisons of pulmonary responses between two different respiratory syncytial virus (RSV) antigenic subgroup A strains, A2 and Line 19. Line 19 strain induced significant dose-responsive airway hyperreactivity (AHR) in BALB/c mice at days 6 and 9 after infection, whereas the A2 strain induced no AHR at any dose. Histological examination indicated that A2 induced no goblet cell hyper/metaplasia, whereas the Line 19 induced goblet cell expansion and significant increases in gob5 and MUC5AC mRNA and protein levels in vivo. When examining cytokine responses, A2 strain induced significant interleukin (IL)-10 expression, whereas Line 19 strain induced significant IL-13 expression. When IL-13-/- mice were infected with Line 19 RSV, the AHR responses were abrogated along with gob5 gene expression. There was little difference in viral titer throughout the infection between the line 19- and A2-infected mice. However, the A2 strain grew to significantly higher titers than the Line 19 strain in HEp-2 cells in vitro. Thus, RSV Line 19-induced airway dysfunction does not correlate with viral load in vivo. These data demonstrate that different RSV strains of the same antigenic subgroup can elicit differential immune responses that impact the phenotypic expression of RSV-induced illness.

Clinical review: respiratory mechanics in spontaneous and assisted ventilation.

Pulmonary disease changes the physiology of the lungs, which manifests as changes in respiratory mechanics. Therefore, measurement of respiratory mechanics allows a clinician to monitor closely the course of pulmonary disease. Here we review the principles of respiratory mechanics and their clinical applications. These principles include compliance, elastance, resistance, impedance, flow, and work of breathing. We discuss these principles in normal conditions and in disease states. As the severity of pulmonary disease increases, mechanical ventilation can become necessary. We discuss the use of pressure–volume curves in assisting with poorly compliant lungs while on mechanical ventilation. In addition, we discuss physiologic parameters that assist with ventilator weaning as the disease process abates.

Disease severity in siblings with cystic fibrosis.

Since cross-infection occurs between cystic fibrosis (CF) siblings, we hypothesized that subsequent siblings may acquire respiratory pathogens at an earlier age and have a more severe course of pulmonary disease. We studied a retrospective cohort of 31 sibling pairs from the CF database at the Hospital for Sick Children. Kaplan-Meier curves and modified log-rank tests were used to test sibling differences in age of acquisition of Pseudomonas aeruginosa (PA), Staphylococcus aureus (SA), or any positive culture. Differences in disease severity outcomes were explored. Older siblings were more likely to have both SA and any CF pathogen first isolated from respiratory culture at an older age than younger siblings (P = 0.0050 and P = 0.0008, respectively, by modified log-rank tests). However, more of the older siblings were positive on first culture at time of diagnosis, introducing an age-of-diagnosis bias. Hospitalization rates, courses of oral antibiotics, FEV(1) % predicted, and weight and height measurements were not better in the older children. No differences in clinical parameters were found between older and younger siblings. The apparent finding of younger age at first isolation of pathogens from respiratory cultures in younger siblings is likely because many older siblings were already infected with these organisms at time of diagnosis.

9 Cystic fibrosis: Nutritional consequences and management

Malnutrition is an adverse prognostic factor in cystic fibrosis, influencing the course of pulmonary disease and correlating inversely with survival. A positive energy balance between energy intake and the combination of total energy expenditure, energy losses and growth-related energy cost is essential to maintain normal nutritional status. Before starting nutritional supplementation, it is important to rule out pathological conditions that may have a deleterious effect on nutritional status: persistent exocrine pancreatic insufficiency, chronic bacterial pulmonary colonization, impaired glucose tolerance, specific nutritional deficits and associated disorders leading to a decrease of energy intake. Several methods are available, ranging from boosted oral nutrition to behavioural intervention, oral supplementation, enteral nutrition and, rarely, parenteral nutrition. The use of elemental nutrients for either oral supplementation or enteral nutrition seems of no nutritional benefit and is more expensive than conventional polymeric nutrients. Provided that the goals of the nutritional supplementation are fulfilled, simpler is often better.

Pulmonary manifestations of scleroderma.

Scleroderma is a severe systemic collagen vascular disease of unknown cause characterized by marked vascular and connective tissue abnormalities. The lungs are commonly involved in scleroderma, ranking only behind the skin, the peripheral vasculature, and the esophagus in frequency of organ involvement. Respiratory symptoms are, in a very few cases, the presenting manifestation of the disease. Abnormalities of pulmonary function in affected patients include a restrictive ventilatory defect, air flow obstruction, and a depressed diffusing capacity for carbon monoxide, which may be an isolated early finding. Interstitial lung disease and honeycombed lung are the most common pulmonary parenchymal abnormalities seen on chest radiographs. Enlargement of the cardiac silhouette and pulmonary artery due to scleroderma-induced pulmonary vascular disease is also noted. High-resolution computed tomography (HRCT) apparently is a sensitive, potentially useful technique for detecting occult interstitial lung disease in patients with scleroderma. Bronchoalveolar lavage usually shows an increase in total cell count and in the percentage of granulocytes; occasionally, there is a predominantly mononuclear (lymphocytic) cell alveolitis. Premortem and postmortem studies reveal two predominant lung lesions: (1) interstitial lung disease and (2) pulmonary vascular disease. Pulmonary vascular disease may occur in the absence of interstitial lung disease, particularly in patients with limited, as opposed to diffuse, scleroderma. The overall mortality rate in scleroderma is 50% at 7 years, and pulmonary complications are the major cause of death. No prospective, well-controlled studies have established that treatment alters the natural course of pulmonary disease in patients with scleroderma. Both D-penicillamine and cyclophosphamide have shown promise for treating patients with interstitial lung disease, and nifedipine may be useful for treating patients with early pulmonary vascular disease.

Cystic fibrosis arthritis. A report of five cases.

In a retrospective study of 206 patients with cystic fibrosis (CF), five cases of CF arthritis were recorded. This is a frequency of 2.5% and of 4.5% in patients aged over 10. Four patients had episodic arthritis, which was related to the course of pulmonary disease in two cases. In three patients, synovial fluid examination revealed minimal evidence of inflammation. In one of these three cases, synovial biopsy revealed a mild and non-specific synovitis. The fifth patient had chronic arthropathy and was positive for rheumatoid factor, but did not fulfil the criteria for rheumatoid arthritis. There were no radiographic abnormalities in any of these cases. CF arthritis is a rare syndrome of unknown pathogenesis.

Nutritional Support of Pulmonary Patients: A Multidisciplinary Approach

Pulmonary disease affects and is affected by the nutritional status of the patient. The relationships between nutrition, medications, complications, and the course of pulmonary disease itself are multifaceted and are the focus of concern for the nutritional support team. Nutritional support of patients with pulmonary disease demands the expertise of a multidisciplinary team in monitoring the nutritional status of patients, appropriately selecting feeding solutions and routines, selecting and administering medications, and planning and implementing nursing interventions. Recognition of the importance of the nutritional component of care for patients with pulmonary disease is the focus of this article.

Discussion

Discussion

Nutritional rehabilitation in cystic fibrosis: Controlled studies of effects on nutritional growth retardation, body protein turnover, and course of pulmonary disease

The effects of a sustained increase in energy and protein intake on weight gain, growth, body protein metabolism, and the course of pulmonary disease were studied in 10 undernourished patients with cystic fibrosis unable to maintain nutrition and growth by the oral route and with declining nutritional and pulmonary status in the year prior to study. A 1-year course of nutrient supplementation using a semielemental high-nitrogen formula was delivered by nocturnal intragastric feeding or as an orally administered supplement; progress was compared with that of 14 height-, sex- and FEV1-matched patients with cystic fibrosis receiving conventional therapy. Supplementation resulted in a catch-up weight gain and sustained improvement in linear growth, with fewer pulmonary infections per year than during the initial observation period. Better weight gain and linear growth than in the comparison group were observed, as well as a significant reversal of the trend for deteriorating lung function. Compared with data from healthy children, 15N-glycine kinetics demonstrated increased protein breakdown and negligible net protein deposition in the treatment group prior to supplementation. After supplementation, synthesis in excess of breakdown, with net protein accretion, occurred by 1 month of supplementation. By 6 to 12 months a significant reduction in the previously high rate of mean synthesis and breakdown was observed, with maintenance of net anabolism. These dynamic changes in whole-body protein turnover reflect a long-term improvement in energy and protein intake, which can favorably affect nutrition, growth, and the course of pulmonary disease in problem cases of cystic fibrosis.