Left Main Bronchus Stenosis Lesion, Neutrophil Count, and Platelet Count Are Predictors of Post-Tuberculosis Bronchomalacia.

BACKGROUND Post-tuberculosis bronchomalacia (PTBM) is one of the main conditions occurring in patients after tracheobronchial tuberculosis (TBTB), and is also associated with the recurrence of symptoms. The present study aimed to investigate the predictors of PTBM in patients who had been undergoing appropriate TB treatment. MATERIAL AND METHODS Clinical data of 104 patients with symptomatic airway stenosis after TBTB between January 01, 2019 and June 31, 2020 were recorded and analyzed. The association between baseline clinical characteristics, laboratory results, and PTBM was calculated with logistical regression. The time from onset of bronchoscopic intervention was examined by Kaplan-Meier estimates; differences between the 2 groups were tested by the log-rank test. RESULTS Fifty-seven patients (54.81%) had PTBM. In the multivariate logistical analysis, the left main bronchus stenosis lesion (odds ratio [OR]=3.763), neutrophil (NEUT) count (OR=1.527), and platelet (PLT) (OR=1.010) count were predictors of PTBM. During follow-up, patients with BM had a significantly longer duration from onset of bronchoscopic intervention than patients without BM (hazard ratio=2.412, P<0.0001). Further, all patients needing long-term bronchoscopic intervention therapy were subsequently identified as having PTBM. Additionally, blood PLT counts were significantly decreased to normal levels in the non-BM group (P<0.05), but not in the BM group (P>0.05). CONCLUSIONS PTBM is most likely to occur in the left main bronchus. The inflammatory and immune responses associated with NEUT and PLT may represent therapeutic targets of PTBM. Our study is the first to report that decreased blood PLT count has the potential to monitor the treatment response.

Microbiological Status as a Factor of Airway Complications After Lung Transplantation.

BACKGROUND: Lung transplantation (LTx) is the only treatment for patients with end-stage lung disease. This procedure is associated with a risk of complications related to airway stenosis, which can be treated by means of bronchoscopic interventions (BI). Microbiological colonization may have an impact on airway complications. The aim of the study was to investigate the effect of presence of microbiological pathogens in graft among lung recipients and frequency of BI, considered as the indicator of severe complications. MATERIALS AND METHODS: The study design was single-center retrospective cohort research; cases of 116 patients with complete microbiological data who underwent LTx from April 2013 to June 2019 were reviewed (70.3% of transplanted patients). All statistical analyses were performed with SPSS version 25.0 and R 3.5.3. For analyses involving the number of bronchoscopy interventions, univariate and multivariate Poisson regression were used. Interaction effect of variables in multivariate Poisson regression was assessed with partial response plot. RESULTS: The mean number of pathogens colonizing each patient was approximately 4.66 (range, 0 to 19) with Candida albicans (n = 42, 36.2%), Aspergillus spp. (n = 33, 28.4%), Pseudomonas aeruginosa (n = 32, 27.59%), and methicillin-sensitive Staphylococcus aureus (MSSA) (n = 29, 25%) being the most prominent. Microbiological agents causing the greatest increase in the risk of intervention are as follows: Proteus mirabilis by 3.84 times, Aspergillus spp. by 3.53 times, and Stenotrophomonas maltophilia by 3.09 times. Burkholderia multivorans, Enterococcus spp., and Klebsiella spp. do not have a statistically significant impact on the number of BI. CONCLUSIONS: Some pathogens increase the frequency of complications, which are associated with deterioration of the general condition. Therefore, patients should be monitored for the presence of pathogens in the airways.

The Value of T-SPOT.TB in Early Diagnosis of Tracheobronchial Tuberculosis.

OBJECTIVE: To evaluate the value of T-SPOT.TB in the diagnosis of tracheobronchial tuberculosis. METHODS: This study included in January 2010 to October 2014 in the three gorges university during the first clinical medical college of final 283 diagnosed with tracheal bronchus TB patients (including 273 patients with pathological biopsy diagnosis and 10 called suspected TB patients), at the same time will be 283 active TB patients as a parallel control group included in this study. They were all given traditional detection methods acid fast stain and diseased tissue pathological biopsy and the new detection method T-SPOT.TB. RESULTS: Sputum smear acid-fast stain sensitivity rate is 39.2% (111/283), typical TB diseased tissue pathology biopsy pathology morphology of 221 cases (78.1%), tend to TB 52 cases (18.4%),while T-SPOT. TB testing sensitivity and speciality rate is 93.6% (265/283) and 85.1% (241/283), which is much higher then the former two. CONCLUSION: T-SPOT.TB can provide important basis for the diagnosis of tracheobronchial tuberculosis.It is the fastest and most accu-rate method in the diagnosis of tracheobronchial tuberculosis.

[Small airway diseases and immune deficiency]. / Atteinte des voies aériennes distales et immunodépression.

INTRODUCTION: Innate or acquired immune deficiency may show respiratory manifestations, often characterized by small airway involvement. The purpose of this article is to provide an overview of small airway disease across the major causes of immune deficiency. BACKGROUND: In patients with common variable immune deficiency, recurrent lower airway infections may lead to bronchiolitis and bronchiectasis. Follicular and/or granulomatous bronchiolitis of unknown origin may also occur. Bronchiolitis obliterans is the leading cause of death after the first year in patients with lung transplantation. Bronchiolitis obliterans also occurs in patients with allogeneic haematopoietic stem cell transplantation, especially in the context of systemic graft-versus-host disease. VIEWPOINT AND CONCLUSION: Small airway diseases have different clinical expression and pathophysiology across various causes of immune deficiency. A better understanding of small airways disease pathogenesis in these settings may lead to the development of novel targeted therapies.

Immune diffuse alveolar hemorrhage: a retrospective assessment of a diagnostic scale.

BACKGROUND: Initiating early steroid treatment in patients with immune diffuse alveolar hemorrhage (DAH) is a key aspect of early management. However, steroid initiation is often delayed until the results of immunological markers and/or tissue biopsy have been obtained, which could contribute to poor outcomes. We previously developed a clinical score allowing for the early diagnosis of DAH of immune causes. However, this score has not been validated in an independent cohort of patients. The aim of this study was to assess the validity of this diagnostic score using an independent cohort of patients admitted for DAH of immune and nonimmune causes. METHODS: We conducted a retrospective cohort study of patients admitted between January 2002 and December 2009 for DAH of immune and nonimmune causes. RESULTS: Forty-six patients were included in the study, with 12 patients having immune DAH and 34 patients with nonimmune DAH. Application of our previously validated clinical scale of immune DAH to this independent population of patients yielded an area under the ROC curve of 0.95 [0.90-1.01]. A score ≥4/10 was associated with the best performances of this scale: sensitivity = 1.00 [0.73-1.00], specificity = 0.88 [0.72-0.97], positive predictive value = 0.75 [0.48-0.93], and negative predictive value = 1.00 [0.88-1.00]. CONCLUSION: While immunological tests and tissue biopsy results are pending, deciding whether to initiate an immunosuppressive treatment is challenging. The initiation of early corticosteroid treatment is warranted in patients with immune DAH and could improve outcomes. This study confirms that this score allows for a good discrimination between patients with immune and nonimmune DAH. Because this series has several limitations, including its single-center and retrospective nature, the small number of patients included, and the lack of therapeutic intervention, a prospective evaluation of this score is warranted to ascertain whether it can improve the adequacy of early treatment strategies and thus improve the outcomes of DAH patients.

[Immunogenetic predisposition to chronic nonspecific inflammatory bowel disease].

Immunology has grown beyond the classic doctrine of immunity to infectious diseases, and gradually covered the problems of general physiology and pathology, genetics, embryology, transplantation, oncology and many other disciplines. A new direction has appeared--immunogenetics, which should help to answer questions the disposition and/or resistance to disease, as well as influence of environmental factors on implementation of predisposition to the development of pathology. Much attention is paid to investigation of HLA in IBD. These data indicate a significant polymorphism of major histocompatibility complex antigens in this disease in different countries. The aim of our study was to investigate the immunogenetic susceptibility and resistance to the development of ulcerative colitis (UC), and Crohn's disease (CD), the character of their flow, as well as the associated extraintestinal manifestations, in particular predisposition development of bronchial obstruction (BO) in patients with inflammatory bowel disease (IBD). A study of DNA frozen blood samples of 75 patients with IBD of both sexes has been conducted. The obtained results have been compared with the results of the study 1700 of samples of umbilical cord blood of newborns (apparently healthy children), born at 37-41 weeks' gestation in Moscow (control). The group of patients with UC revealed a positive association of HLA specificities-B*38, HLA-Cw*12 and HLA-DRV1*15, which can be regarded as potentially high risk of developing the disease. The presence of the specificity of HLA-DQV1*02 can be considered as a factor in resistance to the development of UC. High risk of developing Crohn's disease among residents of Moscow associated with groups of alleles of HLA B*41, HLA-B*56, HLA-Cw*05, HLA-Cw*08, HLA-DRV1*01, HLA-DRV1*11, HLA-DQV1*04, and the presence of specificity of HLA-DQV1*05 can be considered as a factor of resistance to the development of BC. High risk of developing BO in patients with IBD is associated with specificities HLA-DQB1*02, DQB1*03, DRB1*15.

Lung disease with anti-CCP antibodies but not rheumatoid arthritis or connective tissue disease.

OBJECTIVE: We sought to characterize a novel cohort of patients with lung disease, anti-cyclic citrullinated peptide (CCP) antibody positivity, without rheumatoid arthritis (RA) or other connective tissue disease (CTD). METHODS: The study sample included 74 subjects with respiratory symptoms, evaluated January 2008-January 2010 and found to have a positive anti-CCP antibody but no evidence for RA or other CTD. Each underwent serologic testing, pulmonary physiology testing, and thoracic high-resolution computed tomography (HRCT) scan as part of routine clinical evaluation. RESULTS: The majority of subjects were women, and most were former cigarette smokers. Four distinct radiographic phenotypes were identified: isolated airways disease (54%), isolated interstitial lung disease (ILD) (14%), mixed airways disease and ILD (26%), and combined pulmonary fibrosis with emphysema (7%). This cohort had a predominance of airways disease, either in isolation or along with a usual interstitial pneumonia-pattern of ILD. Among subjects with high-titer anti-CCP positivity (n=33), three developed the articular manifestations of RA during a median follow-up of 449 days. CONCLUSION: We have described a unique cohort of patients with anti-CCP antibody positivity and lung disease in the absence of existing RA or other CTD. The lung phenotypic characteristics of this cohort resemble those of established RA and a few of these patients have developed articular RA within a short period of follow-up. The implications of a positive anti-CCP antibody among patients with lung disease but not RA are not yet known, but we believe requires further investigation.

Brief report: airways abnormalities and rheumatoid arthritis-related autoantibodies in subjects without arthritis: early injury or initiating site of autoimmunity?

OBJECTIVE: To evaluate the presence of pulmonary abnormalities in rheumatoid arthritis (RA)-related autoantibody-positive subjects without inflammatory arthritis. METHODS: Forty-two subjects who did not have inflammatory arthritis but were positive for anti-cyclic citrullinated peptide antibodies and/or ≥2 rheumatoid factor isotypes (a profile that is 96% specific for RA), 15 autoantibody-negative controls, and 12 patients with established seropositive early RA (<1-year duration) underwent spirometry and high-resolution computed tomography (HRCT) lung imaging. RESULTS: The median age of autoantibody-positive subjects was 54 years, 52% were female, and 38% were ever-smokers; these characteristics were not significantly different from those of autoantibody-negative control subjects. No autoantibody-positive subject had inflammatory arthritis based on joint examination. HRCT revealed that 76% of autoantibody-positive subjects had airways abnormalities including bronchial wall thickening, bronchiectasis, centrilobular opacities, and air trapping, compared with 33% of autoantibody-negative controls (P = 0.005). The prevalence and type of lung abnormalities among autoantibody-positive subjects were similar to those among patients with early RA. In 2 autoantibody-positive subjects with airways disease, inflammatory arthritis classifiable as articular RA developed ∼13 months after the lung evaluation. CONCLUSION: Airways abnormalities that are consistent with inflammation are common in autoantibody-positive subjects without inflammatory arthritis and are similar to airways abnormalities seen in patients with early RA. These findings suggest that the lung may be an early site of autoimmune-related injury and potentially a site of generation of RA-related autoimmunity. Further studies are needed to define the mechanistic role of lung inflammation in the development of RA.

IgG4-related airway involvement which developed in a patient receiving corticosteroid therapy for autoimmune pancreatitis.

A 66-year-old man was diagnosed with autoimmune pancreatitis in February 2009 and started 40 mg of oral prednisolone followed by a maintenance dose of 5 mg daily. The patient developed a cough in October 2010 and visited our division. He had a high serum concentration of immunoglobulin (Ig) G4 and his chest computed tomography showed airway stenosis without bilateral hilar lymphadenopathy (BHL). The bronchial biopsy specimens revealed lymphoplasmacytic infiltrations with IgG4-positive/IgG-positive plasma cells of more than 50%. Thus, we diagnosed the airway lesion with IgG4-related airway involvement. This is the first report of a patient with IgG4-related airway involvement without BHL.

[Experimental model of broncho-pulmonary diseases formation under exposure to dust of biologic origin].

The article covers results of experimental study of bronchopulmonary system under exposure to biologic dust. The authors revealed some features of pathogenetic mechanisms underlying formation of broncho-pulmonary diseases under exposure to biologic dust.

Mucoid impaction after segmental resection of lung.

Lung segmentectomy is generally considered as a standard procedure in general thoracic surgery. Anatomical variations of pulmonary segmentation may, however, make it difficult to determine the precise area of resection during segmentectomy. Incomplete pulmonary sub-lobar resection may produce unusual radiographic features. Herein, we report a case of bronchial atresia after lung segmentectomy.

Epidemiology and clinical significance of pneumocystis colonization.

Pneumocystis pneumonia has long been recognized as a cause of morbidity and mortality in immunocompromised populations, particularly those with HIV infection. Pneumocystis colonization-that is, detection of the organism or its DNA, without signs or symptoms of pneumonia-has recently been described, and accumulating evidence suggests that it may be an important clinical phenomenon. Sensitive molecular techniques such as polymerase chain reaction are frequently used to identify Pneumocystis colonization. Low levels of Pneumocystis in the lungs may stimulate pulmonary inflammation and may play a role in the development of lung diseases such as chronic obstructive pulmonary disease. In this review, we discuss evidence for the occurrence of Pneumocystis colonization in animals as well as the epidemiology and risk factors for Pneumocystis colonization in various human populations. We also evaluate the clinical significance of Pneumocystis colonization and its relationship to lung disease.

[The role of interleukin-18 in the pathogenesis of bronchial asthma and other allergic diseases and in activation of basophils and mastocytes]. / Rola interleukiny 18 w patogenezie astmy oskrzelowej i innych chorób alergicznych oraz aktywacji bazofilów i mastocytów.

Interleukin-18 is a proinflammatory cytokine produced by a wide range of cells and is involved in the pathogenesis of several inflammatory diseases such as atopic asthma. It was recently demonstrated that IL-18 acts on T cells to induce airway inflammation and airway hyperresponsiveness. These observations strongly indicate that IL-18 stimulates Th1 cells to produce cytokines and chemokines responsible for the airway infiltration and inflammatory responsiveness. Moreover IL-18 activates mast cells and basophils playing the important role in atopy. Atopic asthma is characterized by eosinophilic airway inflammation, remodeling, mucus hypersecretion and high serum levels of IgE. Most current data suggest that asthma drives development of a Th2 lymphocyte-predominant immune response, which is associated with atopy and IgE mediated inflammation via pathways involving the production of proinflammatory cytokines such as IL-18. Here we discuss the functional role of IL-18 in activation of mast cells and basophils and pathogenesis of allergic diseases.

Allergic airways disease develops after an increase in allergen capture and processing in the airway mucosa.

Airway mucosal dendritic cells (AMDC) and other airway APCs continuously sample inhaled Ags and regulate the nature of any resulting T cell-mediated immune response. Although immunity develops to harmful pathogens, tolerance arises to nonpathogenic Ags in healthy individuals. This homeostasis is thought to be disrupted in allergic respiratory disorders such as allergic asthma, such that a potentially damaging Th2-biased, CD4(+) T cell-mediated inflammatory response develops against intrinsically nonpathogenic allergens. Using a mouse model of experimental allergic airways disease (EAAD), we have investigated the functional changes occurring in AMDC and other airway APC populations during disease onset. Onset of EAAD was characterized by early and transient activation of airway CD4(+) T cells coinciding with up-regulation of CD40 expression exclusively on CD11b(-) AMDC. Concurrent enhanced allergen uptake and processing occurred within all airway APC populations, including B cells, macrophages, and both CD11b(+) and CD11b(-) AMDC subsets. Immune serum transfer into naive animals recapitulated the enhanced allergen uptake observed in airway APC populations and mediated activation of naive allergen-specific, airway CD4(+) T cells following inhaled allergen challenge. These data suggest that the onset of EAAD is initiated by enhanced allergen capture and processing by a number of airway APC populations and that allergen-specific Igs play a role in the conversion of normally quiescent AMDC subsets into those capable of inducing airway CD4(+) T cell activation.

[Radiographic presentation of the bronchial and pulmonary changes in children with selected primary immunodeficiencies]. / Obraz radiologiczny przewleklych zmian oskrzelowych i plucnych u dzieci z wybranymi pierwotnymi niedoborami odpornosci.

In the paper authors presented issues concerning clinical manifestation of primary immunodeficiency diseases in children. Considering the frequently recognized changes in the respiratory tract in this group of disorders, particular attention was paid to the chronic bronchopulmonary disease taking into consideration it's clinical course and radiographic presentation in selected cases.

IL-21 receptor signaling is integral to the development of Th2 effector responses in vivo.

Interleukin 21 (IL-21) is a member of the common gamma-chain family of cytokines, which influence a broad spectrum of immunologic responses. A number of studies have examined the function of IL-21, but its specific role in Th1/Th2-cell differentiation and related effector responses remains to be clarified. Thus, we generated IL-21R-deficient mice and have investigated the role of IL-21R signaling using a series of in vivo experimentally induced disease models. We first addressed the role of IL-21R signaling in Th2 immune responses by examining allergic airway inflammation, and Nippostrongylus brasiliensis and Heligmosomoides polygyrus antihelminth responses. In each of these systems, IL-21R signaling played a clear role in the development of Th2 responses. Comparatively, IL-21R signaling was not required for the containment of Leishmania major infection or the development of experimental autoimmune myocarditis, indicative of competent Th1 and Th17 responses, respectively. Adoptive transfer of T cells and analysis of IL-21R+/+/IL-21R-/- chimera mice revealed that IL-21R-signaling was central to Th2-cell survival or migration to peripheral tissues. Overall, our data show IL-21 plays a crucial role in supporting polarized Th2 responses in vivo, while appearing superfluous for Th1 and Th17 responses.