What Does The Time Factor Teach Us In Severe Pneumonia?

To evaluate the effectiveness and safety of zinc supplementation as adjuvant in treatment of pneumonia. Ninety-eight children with acute bacterial pneumonia, aged between 2 months to 5 years, were studied in a randomized controlled single blind design. They received either zinc supplementation, as zinc acetate syrup, or placebo, as vitamin B-complex syrup, for 14 days, concomitantly with antimicrobial treatment (49 per group). Chest radiograph and blood tests were done for confirmation of diagnosis and severity of pneumonia was assessed by breathing rate, chest in-drawing and body temperature. Potentially immunosuppressed children or those with serious comorbidity were excluded. Follow-up was done daily while subjects were admitted (generally 7 days) and the final assessment made on the 14th day on out-patient basis. Children enrolled in zinc and placebo groups were of comparable age [17 ± 10 and 10 ± 30 months (median ± interquartile range) respectively] and sex distribution [34 (69.4%) vs 31 (63.3%) males respectively]. Duration of illness at diagnosis was also comparable. Patients supplemented with zinc showed no difference in clinical cure rate at 14 days when compared with placebo. Fast breathing was present after 1 wk of treatment in 49% subjects in zinc supplemented vs 43% on placebo (p = 0.685). There was also no difference in breathing rate at study end. Regarding fever, the mean temperature was <99°F in both groups at study end. Hemoglobin, total leukocyte count, standard liver function tests and creatinine showed no difference between groups either at baseline or at study end. There were no treatment emergent adverse events attributable to zinc. Though well tolerated; the addition of zinc does not improve symptom duration or cure rate in acute bacterial pneumonia in under-five children.

The study aimed to evaluate the efficacy of zinc supplementation, in addition to standard antimicrobial therapy, in the treatment of severe pneumonia among hospitalized rural Indian children aged 2-24 months. It also sought to identify factors associated with the development of pneumonia in this population. A hospital-based, randomized, double-blinded, placebo-controlled trial was conducted from September to December 2022, registered with the Clinical Trial Registry of India (CTRI/2022/09/046070). A total of 94 children with severe pneumonia were randomly assigned to receive either 10 mg of zinc gluconate (2.5 ml) or a placebo twice daily during hospitalization, along with standard therapy. Clinical signs, symptoms, and laboratory parameters were monitored, and baseline characteristics were compared between the groups. The median duration of cough and cold in the Zinc group was significantly shorter compared to the Control group (p = 0.013, p = 0.005, respectively). Among stunted children, those in the Zinc group required about 3.12 fewer days for recovery compared to those in the Control group, and this difference was statistically significant (p = 0.05). However, no statistically significant differences were observed between the groups in the duration of tachypnea, hypoxia, chest indrawing, inability to feed, lethargy, severe illness, or overall hospitalization. While zinc supplementation demonstrated potential benefits such as reduced hospital stay and faster symptom resolution, these differences were not statistically significant. Further research is needed to validate zinc role in improving clinical outcomes in severe pediatric pneumonia.

BackgroundThis study aimed to investigate the association between e-cigarette (EC) use and development of acute severe pneumonia in the Korean population using a national database.MethodsWe conducted a retrospective analysis using linkage of data between the Korean National Health and Nutrition Examination Survey (KNHANES) and the National Health Insurance Service (NHIS) administrative claims database. The primary endpoint of this study was development of severe pneumonia requiring hospital admission according to EC use during the study period. The secondary endpoints were in-hospital mortality, intensive care unit (ICU) admission, ventilator care, and days of hospital stay.ResultsThe final analysis included 28,950 individuals, of which 578 (2.0%) were EC users. EC users were younger and more often male than non-EC users. The EC users showed higher level of education and household income and had fewer comorbidities. Severe pneumonia was noted in 37 of 28,372 non-EC users (0.13%), but there were no occurrences of severe pneumonia in EC users. The incidence of pneumonia occurrence was not different between the two groups (P = 1.000).ConclusionsSince e-cigarette or vaping use-associated lung injury (EVALI) is most likely included in acute severe pneumonia occurring within 3 months of EC use, it is considered that there might be no EVALI patients in Korea during the investigation period. A large-scale, prospective study is necessary to evaluate the association between EC use and acute lung injury.

Objective To investigate the changes of plasma microRNA-223 (miR-223) in pediatric severe pneumonia patients and its relationship with severe pneumonia. Methods There were 50 children with severe pneumonia enrolled in the study (observation group), and 50 healthy children were selected as control group (normal control group). The expression levels of plasma miR-223 were detected by real time polymerase chain reaction.The relationship between miR-223 and procalcitonin (PCT), C-reactive protein (CRP), tumor necrosis factor-α (TNF)-α, and interleukin (IL)-10 were analyzed. The predictive value of miR-223 in plasma, PCT, and CRP to severe pneumonia was evaluated by receiver operating characteristic (ROC) curve. The relationship between miR-223, T cells, TNF-α, and IL-10 was analyzed. Results The plasma miR-223 expression levels in observation group were upregulated compared to those in the normal control group[(16.01±5.17)×10-4 mg/L vs (5.44±2.21)×10-4 mg/L, t=7.46, P<0.01]. The CRP and PCT expression levels in severe pneumonia patients were higher than those of the normal control group[z=5.496, 5.198, P<0.05, or P<0.01]. The expressions of CD4+ CD25+ Treg, miR-223, and IL-10 in observation group were higher than those of normal control group (P<0.05). The expression of CD4+ CD25+ Treg, miR-223, and IL-10 in the death children were higher. There was a positive correlation between miR-223 and IL-10 (r=0.335, 0.571, P<0.01). The sensitivity and specific degrees to predict the severe pneumonia in mir-223, PCT, and CRP were 83.79%, 86.12%, 66.68%, 91.05%, 78.01%, and 44.23%, respectively. miR-223 was better than PCT and CRP to predict severe pneumonia in children. Conclusions The expression levels of plasma miR-223 in children with severe pneumonia could reflect the immunity, and it can be used as early prognostic markers to reflect the severity of inflammation in some degree. Key words: MicroRNAs/ME; Pneumonia/ME; Prognosis

Severe pneumonia in infants who are HIV-infected is a common problem in many parts of the developing world, especially sub-Saharan Africa. It has emerged that the condition of severe hypoxic pneumonia in early infancy is a disease of many causes, most occurring together in the individual patient [1-3]. A frequent cause of severe pneumonia in infants is Pneumocystis jiroveci. This condition is usually diagnosed clinically and managed as ‘Pneumocystis pneumonia’ in the regions of the world where HIV-infected children live. Only in the last few years, has it become possible to make a microbiological diagnosis of Pneumocystis jiroveci based on Polymerase Chain Reaction (PCR) testing of airway secretions. However, in the developing world, such testing is largely unavailable and the clinical condition still poses an enormous problem. Pneumocystis jiroveci is a fungal organism that has a predilection for the immune-compromised host, and is a common pathogen in HIV-infected infants. The term PCP (pneumocystis pneumonia) was retained when Pneumocystis carinii was taxonomically renamed jiroveci [4]. Since the earliest reports of HIV infection, PCP has been recognized as a severe form of acute pneumonia. The disease may occur at any age, but is particularly common in early infancy [5]. PCP is recognized clinically by a distinct set of common criteria; hypoxic pneumonia, few pulmonary crackles, a reticular-nodular appearance on chest radiographs and an elevated lactate dehydrogenase (>500

Kinin generation in acute pneumonia and chronic bronchitis.

Introduction. Patients in the intensive care unit (ICU) are likely to suffer from acute respiratory failure (ARF) with a risk of developing acute lung injury (ALI) and its more severe condition, acute respiratory distress syndrome (ARDS) with 30 - 50% mortality. Evidence shows, that important role in ARDS pathophysiology may play an imbalance between oxidant and antioxidant species. Oxidative stress is well established in adult critical illnesses characterized by systemic inflammatory response. Aim of the study was to investigate the influence of oxidative stress species on developing of acute respiratory distress syndrome in patients at risk. Materials and methods. The study was conducted in Pauls Stradins Clinical University Hospital ICU during 6 months in 2013 and approved by ethics committee. There were included 15 ARDS risk patients over 18 years of age with mechanical lung ventilation (MLV) over 24 hours and massive blood component transfusions, acute severe pancreatitis, pneumonia or sepsis. Blood samples were taken three times during observational period- first sample were taken just exactly after inclusion, second sample- on 4th and the last sample- on 7th day after inclusion. The developing of ARDS were diagnosed using revised diagnostic criteria according to the Berlin definition. Reactive oxygen species were measured in plasma using manual or automatic spectrophotometry. Results. Among included patients 82.4 % were males with the mean age 49.3 years, for female 67 years. The most popular diagnosis was acute severe pneumonia (n= 5; 33.3 %), followed by patients with sepsis (n= 4; 26.7%) and acute severe pancreatitis (n= 4; 26.7%). The most informative marker of oxidative stress among all ARDS risk patients is GPx, which correlates with PaO2/ FiO2 and oxidation index (R= -0.52; p= 0.045 and R= 0.57; p= 0.027) at the 1st day of observation. At the 4th day of observation GPx shows statistically significant relation with the level of PEEP (R= 0.57; p= 0.033). Among ARDS patients we have found correlation between PaO2/FiO2 ratio and MDA+ HNE plasma levels (R= 0.69; p= 0.026) at the 1st day of observation. Conclusion. Reactive oxygen substances causing oxidative stress shows a dynamic changes in ARDS patients. The changes of some oxidative markers are related to the increased level of hypoxemia and PEEP used in treatment of ARDS patients.

The role of IL-17A/IL-17RA and lung injuries in children with lethal non-pandemic acute viral pneumonia

Comparable inflammatory processes are activated during the acute respiratory distress syndrome (ARDS) and pneumonia. Although required in most patients with ARDS and patients with severe pneumonia, mechanical ventilation is potentially harmful because it may cause local inflammation by itself (so-called ventilator-induced lung injury, VILI). Interestingly, VILI involves the same inflammatory mechanisms as for ARDS and pneumonia.

Bronchoalveolar lavage findings in severe community-acquired pneumonia due to Legionella pneumophila serogroup 1

Background and Objectives: The coronavirus (SARS-CoV-2) damages all systems and organs. Yet, to a greater extent, the lungs are particularly involved, due to the formation of diffuse exudative inflammation in the form of acute respiratory distress syndrome (ARDS) with next progression to pulmonary fibrosis. SARS-associated lung damage is accompanied by the pronounced activation of mononuclear cells, damage of the alveoli and microvessels, and the development of organized pneumonia. To study the expression of macrophage markers (CD68 and CD163), angiotensin-converting enzyme-2 (ACE2), and caspase-3 on the results of two fatal clinical observations of COVID-19. Materials and Methods: In both clinical cases, the female patients died from complications of confirmed COVID-19. Conventional morphological and immunohistochemical methods were used. Results: There was an acute exudative hemorrhagic pneumonia with the formation of hyaline membranes, focal organization of fibrin, stromal sclerosis, stasis, and thrombus formation in the lung vessels. Signs such as the formation of hyaline membranes, organization, and fibrosis were more pronounced in severe disease activity. The activation of CD68+/CD163+ macrophages could cause cell damage at an early stage of pneumonia development, and subsequently cause fibrotic changes in lung tissue. ACE2 expression in lung tissue was not detected in severe pneumonia, while in moderate pneumonia, weak expression was noted in individual cells of the alveolar epithelium and vascular endothelium. Conclusions: This finding could show the dependence of ACE2 expression on the severity of the inflammatory process in the lungs. The expression of caspase-3 was more pronounced in severe pneumonia.

In patients with severe community-acquired pneumonia, treatment failure is associated with excessive inflammatory response and worse outcomes. Corticosteroids may modulate cytokine release in these patients, but the benefit of this adjunctive therapy remains controversial. To assess the effect of corticosteroids in patients with severe community-acquired pneumonia and high associated inflammatory response. Multicenter, randomized, double-blind, placebo-controlled trial conducted in 3 Spanish teaching hospitals involving patients with both severe community-acquired pneumonia and a high inflammatory response, which was defined as a level of C-reactive protein greater than 150 mg/L at admission. Patients were recruited and followed up from June 2004 through February 2012. Patients were randomized to receive either an intravenous bolus of 0.5 mg/kg per 12 hours of methylprednisolone (n = 61) or placebo (n = 59) for 5 days started within 36 hours of hospital admission. The primary outcome was treatment failure (composite outcome of early treatment failure defined as [1] clinical deterioration indicated by development of shock, [2] need for invasive mechanical ventilation not present at baseline, or [3] death within 72 hours of treatment; or composite outcome of late treatment failure defined as [1] radiographic progression, [2] persistence of severe respiratory failure, [3] development of shock, [4] need for invasive mechanical ventilation not present at baseline, or [5] death between 72 hours and 120 hours after treatment initiation; or both early and late treatment failure). In-hospital mortality was a secondary outcome and adverse events were assessed. There was less treatment failure among patients from the methylprednisolone group (8 patients [13%]) compared with the placebo group (18 patients [31%]) (P = .02), with a difference between groups of 18% (95% CI, 3% to 32%). Corticosteroid treatment reduced the risk of treatment failure (odds ratio, 0.34 [95% CI, 0.14 to 0.87]; P = .02). In-hospital mortality did not differ between the 2 groups (6 patients [10%] in the methylprednisolone group vs 9 patients [15%] in the placebo group; P = .37); the difference between groups was 5% (95% CI, -6% to 17%). Hyperglycemia occurred in 11 patients (18%) in the methylprednisolone group and in 7 patients (12%) in the placebo group (P = .34). Among patients with severe community-acquired pneumonia and high initial inflammatory response, the acute use of methylprednisolone compared with placebo decreased treatment failure. If replicated, these findings would support the use of corticosteroids as adjunctive treatment in this clinical population. clinicaltrials.gov Identifier: NCT00908713.

Expression of pro-inflammatory cytokines by flow-sorted alveolar macrophages in severe pneumonia

Nuclear factor-kappaB(NF-kB) is a group of pleiotropic transcription factors. NF-kB proteins play pivotal roles in immune and inflammatory responses. The pathophysiology of severe pneumonia involves complex cytokine and inflammatory mediator networks. NF-kB activation is a central molecular event leading to activation of these net-works and development of severe pneumonia. Importantly,blockade of NF- kB pathway corrects the pathological abnormalities and improves outcome of severe pneumonia. The critical role of NF-kB activation in severe pneumonia pathophysiology and the effectiveness of inhibiting NF-kB activation in correcting severe pneumonia abnormalities indicate that targeting NF-kB is a desired therapeutic strategy for treatment of severe pneumonia. Key words: Nuclear factor-kappaB; Severe pneumonia; Inhibitors of nuclear factor-kappaB

Previous studies have shown that microRNA is involved in regulating a variety of human inflammatory diseases. The purpose of this study was to investigate the expression of miR-10a-3p in the blood of patients with severe pneumonia and evaluate its value in the diagnosis and prognosis of severe pneumonia. Seventy patients with severe pneumonia and 75 healthy individuals were included in this study. Venous blood of all subjects was obtained for RT-qPCR analysis to obtain the relative expression level of miR-10a-5p. The diagnostic accuracy of miR-10a-5p for severe pneumonia was assessed by ROC curve. After standardized treatment, the prognosis of patients with severe pneumonia was analyzed by a 28-day follow-up method. Kaplan-Meier curve and multivariate Cox regression analysis were used to determine the basic factors influencing the prognosis of patients. Compared with healthy control, serum miR-10a-3p expression in patients with severe pneumonia was distinctly upregulated (P < 0.001). Besides, ROC analysis showed that miR-10a-3p had high diagnostic accuracy for severe pneumonia, with an AUC of 0.881, sensitivity and specificity of 75.7% and 84.0%, respectively. Kaplan-Meier curve exhibited that high miR-10a-3p expression group had a higher probability of death than those with low miR-10a-3p expression. Multivariate Cox regression analysis demonstrated that miR-10a-3p and CRP were independent risk factors affecting the prognosis of patients. The expression of miR-10a-3p was increased in patients with severe pneumonia, and abnormally expressed miR-10a-3p has the potential to be used as a diagnostic and prognostic marker for severe pneumonia, which provides a new biological direction for the early detection and risk assessment of severe pneumonia.