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BACKGROUND: Chronic obstructive pulmonary disease (COPD) exhibits considerable progression heterogeneity. We hypothesized that elastic principal graph analysis (EPGA) would identify distinct clinical phenotypes and their longitudinal relationships. METHODS: Cross-sectional data from 8,972 tobacco-exposed COPDGene participants, with and without COPD, were used to train a model with EPGA, using thirty clinical, physiologic and CT features. Principal component analysis (PCA) was used to reduce data dimensionality to six principal components. An elastic principal tree was fitted to the reduced space. 4,585 participants from COPDGene Phase 2 were used to test longitudinal trajectories. 2,652 participants from SPIROMICS tested external reproducibility. RESULTS: Our analysis used cross-sectional data to create an elastic principal tree, where the concept of time is represented by distance on the tree. Six clinically distinct tree segments were identified that differed by lung function, symptoms, and CT features: 1) Subclinical (SC); 2) Parenchymal Abnormality (PA); 3) Chronic Bronchitis (CB); 4) Emphysema Male (EM); 5) Emphysema Female (EF); and 6) Severe Airways (SA) disease. Cross-sectional SPIROMICS data confirmed similar groupings. 5-year data from COPDGene mapped longitudinal changes onto the tree. 29% of patients changed segment during follow-up; longitudinal trajectories confirmed a net flow of patients along the tree, from SC towards Emphysema, although alternative trajectories were noted, through airway disease predominant phenotypes, CB and SA. CONCLUSION: This novel analytic methodology provides an approach to defining longitudinal phenotypic trajectories using cross sectional data. These insights are clinically relevant and could facilitate precision therapy and future trials to modify disease progression.

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The system of nitric oxide synthases (NOSs) is comprised of three isoforms: nNOS, iNOS, and eNOS. The roles of NOSs in respiratory diseases in vivo have been studied by using inhibitors of NOSs and NOS-knockout mice. Their exact roles remain uncertain, however, because of the non-specificity of inhibitors of NOSs and compensatory up-regulation of other NOSs in NOS-KO mice. We addressed this point in our triple-n/i/eNOSs-KO mice. Triple-n/i/eNOSs-KO mice spontaneously developed pulmonary emphysema and displayed exacerbation of bleomycin-induced pulmonary fibrosis as compared with wild-type (WT) mice. Triple-n/i/eNOSs-KO mice exhibited worsening of hypoxic pulmonary hypertension (PH), which was reversed by treatment with sodium nitrate, and WT mice that underwent triple-n/i/eNOSs-KO bone marrow transplantation (BMT) also showed aggravation of hypoxic PH compared with those that underwent WT BMT. Conversely, ovalbumin-evoked asthma was milder in triple-n/i/eNOSs-KO than WT mice. These results suggest that the roles of NOSs are different in different pathologic states, even in the same respiratory diseases, indicating the diversity of the roles of NOSs. In this review, we describe these previous studies and discuss the roles of NOSs in respiratory health and disease. We also explain the current state of development of inorganic nitrate as a new drug for respiratory diseases.

Asunto(s)

Ratones Noqueados , Animales , Ratones , Óxido Nítrico Sintasa/metabolismo , Óxido Nítrico Sintasa/genética , Humanos , Óxido Nítrico Sintasa de Tipo III/metabolismo , Óxido Nítrico Sintasa de Tipo III/genética , Hipertensión Pulmonar/genética , Hipertensión Pulmonar/metabolismo , Fibrosis Pulmonar/genética , Fibrosis Pulmonar/metabolismo , Fibrosis Pulmonar/patología

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An 18-year-old healthy male complained of a 7-day history of fever, cough, and sore throat, along with a three-day history of left facial swelling. The x-rays revealed subcutaneous emphysema in the chest, neck, face, and mediastinum region (Pneumomediastinum). Furthermore, an area of infiltration was visible, indicating pneumonia. Therefore, we immediately started him on intravenous antibiotics. We then moved the patient to an isolation room, considering pulmonary tuberculosis as one of the differential diagnoses. However, the Acid Fast Bacilli (AFB), Mycobacterium Tuberculosis Bacteria-Polymerase Chain Reaction (MTB PCR), and sputum for gram stain and culture were all negative. On the other hand, the test for parainfluenza virus 3 was positive. The patient was observed with a daily chest x-ray to monitor the progress of pneumonia and subcutaneous emphysema. Fortunately, the subcutaneous emphysema was significantly reduced on a daily basis until it was completely resolved before discharge home.

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Even with recent advances in pathobiology and treatment options, chronic obstructive pulmonary disease (COPD) remains a major contributor to morbidity and mortality. To develop new ways of combating this disease, breakthroughs in our understanding of its mechanisms are sorely needed. Investigating the involvement of underanalyzed lung cell types, such as endothelial cells (ECs), is one way to further our understanding of COPD. JCAD is a junctional protein in endothelial cells (ECs) arising from the KIAA1462 gene, and a mutation in this gene has been implicated in the risk of developing COPD. In our study, we induced inflammation and emphysema in mice via the global knockout of KIAA1462/JCAD (JCAD-KO) and confirmed it in HPMECs and A549 to examine how the loss of JCAD could affect COPD development. We found that KIAA1462/JCAD loss reduced acute lung inflammation after elastase treatment. Even after 3 weeks of elastase, JCAD-KO mice demonstrated a preserved lung parenchymal structure and vasculature. In vitro, after KIAA1462 expression is silenced, both endothelial and epithelial cells showed alterations in pro-inflammatory gene expression after TNF-α treatment. We concluded that JCAD loss could ameliorate COPD through its anti-inflammatory and anti-angiogenic effects, and that KIAA1462/JCAD could be a novel target for COPD therapy.

Asunto(s)

Células Endoteliales , Pulmón , Ratones Noqueados , Enfermedad Pulmonar Obstructiva Crónica , Animales , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/patología , Enfermedad Pulmonar Obstructiva Crónica/etiología , Enfermedad Pulmonar Obstructiva Crónica/genética , Ratones , Humanos , Células Endoteliales/metabolismo , Pulmón/patología , Pulmón/metabolismo , Células A549 , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad

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How to cite this article: Bhosale SJ, Joshi M, Dhakne P, Kulkarni AP. Emphysematous Gastritis: An Ominous Condition Masquerading as Enterocolitis in Immunocompromised Host. Indian J Crit Care Med 2024;28(8):808-809.

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Background: With increasing significance of lung cancer screening programs, it is essential to determine the group of participants, who would benefit the most from screening. In our study, we aimed to establish the correlation between lung emphysema and lung cancer risk. Methods: The study design was cross-sectional. Low-dose computed tomography (LDCT) scans of 896 subjects from MOLTEST-BIS lung cancer screening program, including 100 subjects with detected lung cancer, were visually evaluated for the presence, type and severity of emphysema. Quantitative emphysema evaluation was performed with Siemens syngo.via Pulmo 3D application. Results: Visually detected presence of centrilobular emphysema (CLE) correlated with male gender (P=0.02), age (P<0.001) and pack-years of smoking (P=0.004), as well as with quantitative assessment of Emphysema Index (EI) (P=0.008), and with emphysema clusters of given size (Clas 1-4) Clas 1, Clas 3 and Clas 4 (P<0.001). Visually assessed severity grade of emphysema correlated with age (P<0.001), pack-years of smoking history (P=0.002) and EI (P<0.001). There was a correlation between lung cancer occurrence and pack-years (P<0.001), age (P<0.001), and presence of CLE (P<0.001) but no correlation with gender (P=0.88) and EI (P=0.32) was found. In the logistic regression model pack-years, age, qualitative severity of CLE and Clas 1 were significant factors correlated with lung cancer occurrence (P<0.001). Conclusions: Qualitative and quantitative emphysema evaluation correlate with each other. Both, presence and severity of CLE correlate with higher incidence of lung cancer. Severity of visually assessed emphysema, age and pack-years of smoking are significant predictors of lung cancer occurrence.

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Spontaneous pneumomediastinum (SPM) is an uncommon condition characterized by air in the interstices of the mediastinum. Management generally involves supportive care; however, if a patient inspires high concentrations of oxygen, the mediastinal air will be absorbed faster. A 23-year-old man who presented with acute-onset breathlessness with a history of more than a year of lower backache was diagnosed with SPM and accompanying ankylosing spondylitis (AS) by a chest CT and spinal MRI and was treated conservatively. This case is being reported for its uniqueness, as SPM with underlying AS is rare.

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Robust quantification of pulmonary emphysema on computed tomography (CT) remains challenging for large-scale research studies that involve scans from different scanner types and for translation to clinical scans. Although the domain shifts in different CT scanners are subtle compared to shifts existing in other modalities (e.g., MRI) or cross-modality, emphysema is highly sensitive to it. Such subtle difference limits the application of general domain adaptation methods, such as image translation-based methods, as the contrast difference is too subtle to be distinguished. Existing studies have explored several directions to tackle this challenge, including density correction, noise filtering, regression, hidden Markov measure field (HMMF) model-based segmentation, and volume-adjusted lung density. Despite some promising results, previous studies either required a tedious workflow or eliminated opportunities for downstream emphysema subtyping, limiting efficient adaptation on a large-scale study. To alleviate this dilemma, we developed an end-to-end deep learning framework based on an existing HMMF segmentation framework. We first demonstrate that a regular UNet cannot replicate the existing HMMF results because of the lack of scanner priors. We then design a novel domain attention block, a simple yet efficient cross-modal block to fuse image visual features with quantitative scanner priors (a sequence), which significantly improves the results.

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Pneumomediastinum is a rare condition defined by the presence of air in the mediastinum. In the absence of traumatic injury, iatrogenic injury, or clear etiology, it is called spontaneous pneumomediastinum (SPM). Spontaneous pneumomediastinum most commonly occurs in younger individuals and has a self-limiting course with a good outcome. The purpose of the present manuscript is to systematically review the existing literature on SPM evaluation and management for updated clinical understanding of this condition. A literature search was conducted of publications about SPM on MEDLINE/PubMed and Google Scholar by identifying all the articles with key search terms "pneumomediastinum" and "spontaneous pneumomediastinum". Inclusion criteria were case series published in English between 1980 and 2023. In total, 24 case series were selected and reviewed to determine presenting symptoms, clinical signs and predisposing factors associated with spontaneous pneumomediastinum. Most patients were male; the average age at diagnosis was 26.3 years. The most common presenting symptoms were chest pain and dyspnea. The most common exam finding was subcutaneous emphysema, in 35.4% of patients. Only 5.9% had the classic Hamman's sign. Risk factors include history of asthma, history of smoking, and recent physical activity. This manuscript presents an extensive review of relevant literature highlighting the diagnosis and essential management of spontaneous pneumomediastinum.

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Asphyxia as a cause of death poses a diagnostic challenge in forensic medicine due to both the diversity of underlying mechanisms, and lack of specific markers. Acute emphysema or acute alveolar dilation have long been debated as potential findings in these asphyxia cases. To further explore the supplementary findings in our forensic asphyxia cases, this study applied lung densitometry to pulmonary postmortem computed tomography (PMCT) data. Twenty asphyxia cases (including hanging (n = 9), manual strangulation (n = 4), ligature strangulation (n = 1), smothering (n = 3), and choking (n = 3)) and 21 matched control cases were analysed using lung densitometry parameters - specifically quantification of low attenuation areas (LAA) and the 15th percentile point of lung density (Perc15). Our data revealed statistically significantly higher lung % volume falling within LAA at -950HU (p = 0.04) and - 910HU (p = 0.043) in the asphyxia cases compared to matched controls. The Perc15 values observed were trending towards a lower attenuation corresponding to a lower density in the asphyxia group, although this result was not statistically significant (p = 0.13). A subgroup analysis highlighted potential differences within the asphyxia categories, notably, higher Perc15 values were observed in the choking cases. In conclusion the results from the study support the existing evidence of low pulmonary density as a potential finding in asphyxia cases and demonstrate the potential of applying lung densitometry on pulmonary postmortem computed tomography data.

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OBJECTIVE: To determine the incidence and predictive factors of lung cancer in rheumatoid arthritis (RA). METHODS: We conducted a retrospective follow-up study of patients who were diagnosed with RA at our institution between April 2001 and December 2022. Pulmonary complications were evaluated using high-resolution computed tomography at RA diagnosis. Patients were followed until the diagnosis of lung cancer, diagnosis of other malignancies, death, loss to follow-up, or the end of the study. RESULTS: Among 771 RA patients, 3.5% were diagnosed with combined pulmonary fibrosis and emphysema (CPFE), 4.9% with interstitial lung disease (ILD) alone, and 6.0% with emphysema alone. During follow-up (mean of 9.3 years), the crude incidence rates of lung cancer per 1,000 patient-years were 2.9 in all patients, 47.8 in CPFE patients, 10.5 in ILD patients, 11.9 in emphysema patients, and 0.8 in patients without these complications. The standardized incidence ratios (95% confidence intervals [CI]) compared with the general population were 2.53 (1.29-3.77) for male patients and 0.89 (0.57-1.16) for female patients. In Fine-Gray regression analysis, adjusted hazard ratios (95% CI) of lung cancer were 13.48 (3.14-57.85) for CPFE, 6.42 (1.42-29.09) for ILD alone, and 4.65 (1.18-18.30) for emphysema alone versus without these complications, and 1.02 (1.01-1.04) per additional 1 pack-year for smoking history. These factors were not associated with the risk of other malignancies. CONCLUSION: Close monitoring of lung cancer is needed for RA patients with smoking history and pulmonary complications, especially CPFE.

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The escalating adoption of laparoscopic surgical techniques has demonstrated their capacity to yield improved clinical outcomes. However, concomitant with the advantages of this minimally invasive approach, certain adverse complications have been reported. In this report, we present a noteworthy case involving a 72-year-old male patient who underwent laparoscopic inguinal hernia repair. The surgical procedure proceeded without noteworthy complications, and the patient maintained hemodynamic stability throughout. However, the post-anesthetic recovery was compromised by the onset of subcutaneous emphysema and bilateral tension pneumothorax. Immediate intervention was imperative, prompting the performance of an emergent needle thoracostomy, subsequently followed by the implementation of a closed drainage system within the thoracic cavity. These interventions proved efficacious in mitigating the patient's distressing symptoms. Although pneumothorax complications in the context of laparoscopic surgery are infrequent, it is imperative for anesthetists to remain vigilant regarding the potential occurrence of subcutaneous emphysema and pneumothorax in the perioperative period. This case underscores the significance of meticulous perioperative monitoring and rapid intervention, particularly in laparoscopic procedures, where the insufflation of carbon dioxide into the abdominal cavity can predispose patients to these rare yet potentially life-threatening complications. Heightened awareness among healthcare providers regarding the possibility of such events is pivotal in ensuring the safety and well-being of surgical patients.

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Emphysematous gastritis is a rare condition with a high mortality rate. We present a rare case of haemorrhagic emphysematous gastritis in a 70-year-old woman with a background of relapsed endometrioid ovarian cancer previously treated with chemotherapy and recent prednisolone use. A CT scan showed a grossly distended stomach with gas in the stomach wall and gas in the gastric and portal veins in the liver. The duodenum and small bowel were not dilated, suggesting gastric outlet obstruction potentially secondary to serosal deposits. Endoscopic evaluation showed an ischaemic oesophagus and posterior wall of the stomach, with necrosis of the greater curve. Histology showed complete loss of the gastric epithelium along with transmural necrosis along with intense acute and chronic inflammation. She was treated conservatively, as she was not fit for surgery due to her co-morbidities. She symptomatically improved and was discharged under the palliative care team. There are no current clear guidelines on treatment approaches. After a patient is haemodynamically stabilised, treatment options currently include surgical intervention (gastrectomy) or conservative options (fluid resuscitation, nasogastric decompression, broad-spectrum antibiotics/antifungals and supportive management). Historically, emphysematous gastritis was conventionally managed surgically. There has been a shift towards conservative management in recent literature, reporting good patient outcomes in patients successfully managed without surgical intervention.

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Inflammatory cell infiltration is a characteristic feature of COPD and correlates directly with the severity of the disease. Interleukin-23 (IL-23) is a pro-inflammatory cytokine that regulates Th-17 inflammation, which mediates many pathophysiological events in COPD. The primary goal of this study was to determine the role of IL-23 as a mediator of key pathologic processes in cigarette smoke-induced COPD. In this study, we report an increase in IL23 gene expression in the lung biopsies of COPD patients compared to controls and identified a positive correlation between IL23 gene expression and disease severity. In a cigarette smoke-induced murine emphysema model, the suppression of IL-23 with a monoclonal blocking antibody reduced the severity of cigarette smoke-induced murine emphysema. Mechanistically, the suppression of IL-23 was associated with a reduction in immune cell infiltration, oxidative stress injury, and apoptosis, suggesting a role for IL-23 as an essential immune mediator of the inflammatory processes in the pathogenesis of CS-induced emphysema.

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BACKGROUND: Because alpha-1 antitrypsin deficiency is severely underrecognized and delayed diagnosis is associated with harm, strategies to enhance early detection of alpha-1 antitrypsin deficiency are needed. METHODS: The study intervention was placing a reminder to test for alpha-1 antitrypsin deficiency within an electronic medical record health maintenance dashboard that houses prompts to providers to implement guideline-based recommendations. This recommendation was for all patients assigned a diagnosis of COPD based on relevant International Classification of Diseases, Tenth Revision codes. The rate of testing for and detecting individuals with alpha-1 antitrypsin deficiency was assessed in 12 one-month intervals before and after implementing the dashboard. RESULTS: After the prompt, whereas testing was still performed in only a small percentage of guideline-concordant instances, the rate of testing for alpha-1 antitrypsin deficiency increased 3.8-fold (ie, from 1.2% to 4.6%, P < .05). This did not result in detection of new patients with alpha-1 antitrypsin deficiency. The rate of testing increased both for alpha-1 antitrypsin serum levels and genotypes in each month after the intervention, though the rate of genotype testing was 2-5-fold lower than the rate of testing for serum level. CONCLUSIONS: The results of this preliminary study of a detection strategy for alpha-1 antitrypsin deficiency show that placing a reminder to test for alpha-1 antitrypsin deficiency when indicated in an electronic medical record health maintenance dashboard significantly increased the frequency of testing. Still, that only 4.6% of those in whom testing for alpha-1 antitrypsin deficiency was indicated were tested in the post-intervention period shows that, as for all other alpha-1 antitrypsin deficiency-targeted detection interventions to date, the impact of the intervention was marginal and that other strategies remain needed to mitigate underrecognition. A focus on combining targeted detection strategies (eg, coupling enhanced awareness with free testing) and population-based screening for alpha-1 antitrypsin deficiency is suggested.

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AIM: To assess the correlation of quantitative data of pulmonary Perfused Blood Volume (PBV) on Dual-Energy CT (DECT) datasets in patients with moderate - severe Pulmonary Emphysema (PE) with Lung Perfusion Scintigraphy (LPS) as the reference standard. The secondary endpoints are the correlation between the CT densitometric analysis and the visual assessment of parenchymal destruction with PBV. MATERIALS AND METHODS: Patients with moderate - severe PE candidate to Lung Volumetric Reduction (LVR), with available a pre-procedural LS and a contrast-enhanced DECT were retrospectively included. DECT studies were performed with a 3rd generation Dual-Source CT and the PBV was obtained with a 3-material decomposition algorithm. The CT densitometric analysis was performed with a dedicated commercial software (Pulmo3D). The Goddard Score was used for visual assessment. The perfusion LS were performed after the administration of albumin macroaggregates labeled with 99mTechnetium. The image revision was performed by two radiologists or nuclear medicine physicians blinded, respectively, to LS and DECT data. The statistical analysis was performed with nonparametric tests. RESULTS: Thirty-one patients (18 males, median age 69 y.o., interquartile range 62-71 y.o.) with moderate - severe PE (Median Goddard Score 14/20 and 31% of emphysematous parenchyma at quantitative CT) candidate to LVR were retrospectively included. The median enhancement on PBV was 17 HU. Significant correlation coefficients were demonstrated between lung PBV and LS, poor in apical regions (Rho = 0.1-0.2) and fair (Rho = 0.3-0.5) in middle and lower regions. No significant correlations were recorded between the CT densitometric analysis, the visual score, and the PBV. CONCLUSIONS: Lung perfusion with PBV on DECT is feasible in patients with moderate - severe PE candidate to LVR, and has a poor to fair agreement with LPS.

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Purpose: The exact link between cognitive impairment (CI) and chronic obstructive pulmonary disease (COPD) is still limited. Thus, we aim to find the relationship and interaction of quantitative CT (QCT), lung function, HIF-1α, and clinical factors with the development of CI among COPD patients. Patients and Methods: A cross-sectional multicentre study was conducted from January 2022 to December 2023. We collected clinical data, spirometry, CT images, and venous blood samples from 114 COPD participants. Cognitive impairment assessment using the Montreal Cognitive Assessment Indonesian version (MoCA-Ina) with a cutoff value 26. The QCT analysis consists of lung density, airway wall thickness, pulmonary artery-to-aorta ratio (PA:A), and pectoralis muscles using 3D Slicer software. Serum HIF-1α analysis was performed using ELISA. Results: We found significant differences between %LAA-950, age, COPD duration, BMI, FEV1 pp, and FEV1/FVC among GOLD grades I-IV. Only education duration was found to correlate with CI (r = 0.40; p < 0.001). We found no significant difference in HIF-1α among GOLD grades (p = 0.149) and no correlation between HIF-1α and CI (p = 0.105). From multiple linear regression, we observed that the MoCA-Ina score was influenced mainly by %LAA-950 (p = 0.02) and education duration (p = 0.01). The path analysis model showed both %LAA and education duration directly and indirectly through FEV1 pp contributing to CI. Conclusion: We conclude that the utilization of QCT parameters is beneficial as it can identify abnormalities and contribute to the development of CI, indicating its potential utility in clinical decision-making. The MoCA-Ina score in COPD is mainly affected by %LAA-950 and education duration. Contrary to expectations, this study concludes that HIF-1α does not affect CI among COPD patients.

Asunto(s)

Disfunción Cognitiva , Subunidad alfa del Factor 1 Inducible por Hipoxia , Pulmón , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/sangre , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico por imagen , Masculino , Estudios Transversales , Femenino , Persona de Mediana Edad , Anciano , Pulmón/fisiopatología , Pulmón/diagnóstico por imagen , Subunidad alfa del Factor 1 Inducible por Hipoxia/sangre , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/etiología , Disfunción Cognitiva/sangre , Disfunción Cognitiva/fisiopatología , Cognición , Volumen Espiratorio Forzado , Valor Predictivo de las Pruebas , Factores de Riesgo , Espirometría , Capacidad Vital , Biomarcadores/sangre , Tomografía Computarizada por Rayos X

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Compared to men, women often develop COPD at an earlier age with worse respiratory symptoms despite lower smoking exposure. However, most preventive, and therapeutic strategies ignore biological sex differences in COPD. Our goal was to better understand sex-specific gene regulatory processes in lung tissue and the molecular basis for sex differences in COPD onset and severity. We analyzed lung tissue gene expression and DNA methylation data from 747 individuals in the Lung Tissue Research Consortium (LTRC), and 85 individuals in an independent dataset. We identified sex differences in COPD-associated gene regulation using gene regulatory networks. We used linear regression to test for sex-biased associations of methylation with lung function, emphysema, smoking, and age. Analyzing gene regulatory networks in the control group, we identified that genes involved in the extracellular matrix (ECM) have higher transcriptional factor targeting in females than in males. However, this pattern is reversed in COPD, with males showing stronger regulatory targeting of ECM-related genes than females. Smoking exposure, age, lung function, and emphysema were all associated with sex-specific differential methylation of ECM-related genes. We identified sex-based gene regulatory patterns of ECM-related genes associated with lung function and emphysema. Multiple factors including epigenetics, smoking, aging, and cell heterogeneity influence sex-specific gene regulation in COPD. Our findings underscore the importance of considering sex as a key factor in disease susceptibility and severity.

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A case is presented of extensive pneumomastia seen on a screening mammogram of an asymptomatic patient who had helium plasma treatment 2 weeks earlier for flabby upper arms. Contribution: Rare complications of subcutaneous emphysema, following helium plasma treatment, have been discussed to highlight that such emphysema is usually self-limiting.