Prevalence of early bacterial co-infection in hospitalized patients with COVID-19 pneumonia: a retrospective study.

Background: Identification of bacterial co-infection is crucial in determining outcomes of patients with coronavirus disease 2019 (COVID-19) pneumonia. The present study aims to evaluate the prevalence and associated factors of early bacterial co-infection in patients with COVID-19 pneumonia. Methods: The present study is a retrospective study. Patients with COVID-19 pneumonia, who were admitted to Siriraj Hospital between April 1 and August 31, 2021, were randomly enrolled and classified as the "Early bacterial co-infection" group, defined by an infection occurring within the first 48 hours after admission, and the "Unlikely early bacterial co-infection" group. Results: A total of 245 patients were enrolled. The prevalence of early bacterial co-infection was 15.5%. Chest X-rays showed characteristic findings for COVID-19 pneumonia in 37.6%. The median Brixia chest X-ray scores and C-reactive protein levels were significantly higher in the Early bacterial co-infection group. The most common causative pathogens included Staphylococcus aureus, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia. Patients with early bacterial co-infection had a significantly higher all-cause mortality compared to the Unlikely early bacterial co-infection group (P=0.012). The Charlson Comorbidity Index ≥4, high level of respiratory support, and mass-liked or diffuse opacities on chest X-rays were independent factors associated with the early bacterial co-infection. Conclusions: The prevalence of early bacterial co-infection in patients with COVID-19 pneumonia was low but it was associated with mortality. There is insufficient evidence to support the empirical use of antibiotics in these patients. A further prospective study is required to confirm the results of the present study.

Telomere dysfunction in alveolar epithelial cells causes lung remodeling and fibrosis.

Telomeres are short in type II alveolar epithelial cells (AECs) of patients with idiopathic pulmonary fibrosis (IPF). Whether dysfunctional telomeres contribute directly to development of lung fibrosis remains unknown. The objective of this study was to investigate whether telomere dysfunction in type II AECs, mediated by deletion of the telomere shelterin protein TRF1, leads to pulmonary fibrosis in mice (SPC-Cre TRF1fl/fl mice). Deletion of TRF1 in type II AECs for 2 weeks increased γH2AX DNA damage foci, but not histopathologic changes in the lung. Deletion of TRF1 in type II AECs for up to 9 months resulted in short telomeres and lung remodeling characterized by increased numbers of type II AECs, α-smooth muscle actin+ mesenchymal cells, collagen deposition, and accumulation of senescence-associated ß-galactosidase+ lung epithelial cells. Deletion of TRF1 in collagen-expressing cells caused pulmonary edema, but not fibrosis. These results demonstrate that prolonged telomere dysfunction in type II AECs, but not collagen-expressing cells, leads to age-dependent lung remodeling and fibrosis. We conclude that telomere dysfunction in type II AECs is sufficient to cause lung fibrosis, and may be a dominant molecular defect causing IPF. SPC-Cre TRF1fl/fl mice will be useful for assessing cellular and molecular mechanisms of lung fibrosis mediated by telomere dysfunction.

miR-34 miRNAs Regulate Cellular Senescence in Type II Alveolar Epithelial Cells of Patients with Idiopathic Pulmonary Fibrosis.

Pathologic features of idiopathic pulmonary fibrosis (IPF) include genetic predisposition, activation of the unfolded protein response, telomere attrition, and cellular senescence. The mechanisms leading to alveolar epithelial cell (AEC) senescence are poorly understood. MicroRNAs (miRNAs) have been reported as regulators of cellular senescence. Senescence markers including p16, p21, p53, and senescence-associated ß-galactosidase (SA-ßgal) activity were measured in type II AECs from IPF lungs and unused donor lungs. miRNAs were quantified in type II AECs using gene expression arrays and quantitative RT-PCR. Molecular markers of senescence (p16, p21, and p53) were elevated in IPF type II AECs. SA-ßgal activity was detected in a greater percentage in type II AECs isolated from IPF patients (23.1%) compared to patients with other interstitial lung diseases (1.2%) or normal controls (0.8%). The relative levels of senescence-associated miRNAs miR-34a, miR-34b, and miR-34c, but not miR-20a, miR-29c, or miR-let-7f were significantly higher in type II AECs from IPF patients. Overexpression of miR-34a, miR-34b, or miR-34c in lung epithelial cells was associated with higher SA-ßgal activity (27.8%, 35.1%, and 38.2%, respectively) relative to control treated cells (8.8%). Targets of miR-34 miRNAs, including E2F1, c-Myc, and cyclin E2, were lower in IPF type II AECs. These results show that markers of senescence are uniquely elevated in IPF type II AECs and suggest that the miR-34 family of miRNAs regulate senescence in IPF type II AECs.

Interstitial lung diseases in the hospitalized patient.

BACKGROUND: Interstitial lung diseases (ILDs) are disorders of the lung parenchyma. The pathogenesis, clinical manifestations, and prognosis of ILDs vary depending on the underlying disease. The onset of most ILDs is insidious, but they may also present subacutely or require hospitalization for management. ILDs that may present subacutely include acute interstitial pneumonia, connective tissue disease-associated ILDs, cryptogenic organizing pneumonia, acute eosinophilic pneumonia, drug-induced ILDs, and acute exacerbation of idiopathic pulmonary fibrosis. Prognosis and response to therapy depend on the type of underlying ILD being managed. DISCUSSION: This opinion piece discusses approaches to differentiating ILDs in the hospitalized patient, emphasizing the role of bronchoscopy and surgical lung biopsy. We then consider pharmacologic treatments and the use of mechanical ventilation in hospitalized patients with ILD. Finally, lung transplantation and palliative care as treatment modalities are considered. The diagnosis of ILD in hospitalized patients requires input from multiple disciplines. The prognosis of ILDs presenting acutely vary depending on the underlying ILD. Patients with advanced ILD or acute exacerbation of idiopathic pulmonary fibrosis have poor outcomes. The mainstay treatment in these patients is supportive care, and mechanical ventilation should only be used in these patients as a bridge to lung transplantation.

Overexpression of inhibitor of DNA-binding 2 attenuates pulmonary fibrosis through regulation of c-Abl and Twist.

Fibrosis is a multicellular process leading to excessive extracellular matrix deposition. Factors that affect lung epithelial cell proliferation and activation may be important regulators of the extent of fibrosis after injury. We and others have shown that activated alveolar epithelial cells (AECs) directly contribute to fibrogenesis by secreting mesenchymal proteins, such as type I collagen. Recent evidence suggests that epithelial cell acquisition of mesenchymal features during carcinogenesis and fibrogenesis is regulated by several mesenchymal transcription factors. Induced expression of direct inhibitors to these mesenchymal transcription factors offers a potentially novel therapeutic strategy. Inhibitor of DNA-binding 2 (Id2) is an inhibitory helix-loop-helix transcription factor that is highly expressed by lung epithelial cells during development and has been shown to coordinate cell proliferation and differentiation of cancer cells. We found that overexpression of Id2 in primary AECs promotes proliferation by inhibiting a retinoblastoma protein/c-Abl interaction leading to greater c-Abl activity. Id2 also blocks transforming growth factor ß1-mediated expression of type I collagen by inhibiting Twist, a prominent mesenchymal basic helix-loop-helix transcription factor. In vivo, Id2 induced AEC proliferation and protected mice from lung fibrosis. By using a high-throughput screen, we found that histone deacetylase inhibitors induce Id2 expression by adult AECs. Collectively, these findings suggest that Id2 expression by AECs can be induced, and overexpression of Id2 affects AEC phenotype, leading to protection from fibrosis.

A case series of sarcoidosis with pulmonary involvement: various clinical and radiographic manifestations.

BACKGROUND: Sarcoidosis is a multisystem granulomatous disease of unknown etiology. The disease is rare in East Asian populations. Patients have many clinical presentations and 90% of patients have pulmonary involvement. There are few reports in Thailand that collected the data about chest imaging and pathological findings of sarcoidosis. MATERIAL AND METHOD: The data of patient with sarcoidosis with pulmonary involvement, who followed-up between September 2008 and December 2011, were retrospectively reviewed. RESULTS: Ten patients with sarcoidosis and pulmonary involvement were reviewed. Three patients presented with abnormal chest x-ray without respiratory symptom or other organ involvement. One patient was suspected to be sarcoidosis secondary to etanercept therapy. The majority of patients had cutaneous involvement. The most common finding on chest x-ray is bilateral hilar lymphadenopathy (90%). Seven patients had stage 2 disease and three patients had stage 1 disease. The diagnoses of all patients were confirmed by histopathology and exclusion of tuberculosis and fungal infection. Spirometry showed normal in seven patients, irreversible obstruction in one patient, and impaired diffusing capacity in six patients. There was no indication of systemic corticosteroids or immunosuppressive drug in most patients. CONCLUSION: Sarcoidosis has various clinical manifestations. The pulmonary and cutaneous involvement is common and the diagnosis is made by a combination of clinical, radiological, and histopathologic findings. The treatment of systemic corticosteroids is not required in most patients. The patients should be regularly followed-up in order to follow the course of disease.

Experience of percutaneous dilatational tracheostomy by using Grigg's technique in Siriraj Hospital.

BACKGROUND: Percutaneous dilatational tracheostomy (PDT) was increasingly performed after the commercial kit was available in 1985. Several studies showed that PDT was equivalent to surgical tracheostomy considering perioperative and long-term complications and PDT was more cost-effective and provide greater feasibility in terms of bedside capacity and nonsurgical operation. MATERIAL AND METHOD: The data of patients who were performed PDT at Division of Respiratory Disease and Tuberculosis, Department of Medicine, Faculty of Medicine Siriraj Hospital were retrospectively reviewed since March 2007 to December 2011. All procedures were done at bedside in intensive care unit or general ward of internal medicine under intravenous anesthesia. PDT was performed by using Griggs' technique. This technique is based on Seldinger guidewire technique and uses the guidewire dilator forceps (GWDFs) to enlarge the hole in the trachea under flexible bronchoscopic visualization. RESULTS: Ninety-one patients were enrolled with a mean age of 68 years old (range 17-100). Majority of patients had American Society of Anesthesiologist (ASA) classification 3. The most common indication for tracheostomy was failure to wean from the mechanical ventilator (68 patients; 74.7%). Fifty-two procedures (57.1%) were done at intensive care unit and 39 procedures (42.9%) were done at general ward of internal medicine. Mean duration of procedure was 18 minutes (range 5-90). The rate of perioperative complication was 11.0%. Five patients (5.5%) had desaturation and all of them were improved by short disruption of the procedure for ventilatory support. Three patients (3.3%) had moderate bleeding and one (1.1 %) had excessive bleeding that were stopped by electrocauterization and pressure compression. There was 1 serious perioperative complication that was accidental extubation. No perioperative or postoperative mortality that related to procedure was found. CONCLUSION: PDT is a safe procedure and can be performed easily and rapidly at the bedside either in intensive care unit or general ward with closed monitoring. Proper patient selection and attention to technical detail are necessary in maintaining low complication rates.

High dose rate endobronchial brachytherapy (HDR-EB) in recurrent benign complex tracheobronchial stenosis: experience in two cases.

UNLABELLED: Benign complex tracheobronchial stenosis (BCTS) is a tracheobronchial stenosis that is longer than 1 cm or has more than one site of stenotic area. The most common etiology of the stenosis is endobronchial tuberculosis. BCTS causes challenge in diagnosis and management because of nonspecific presentation and usually precluded surgical treatment. Available interventional bronchoscopic techniques fail to manage BCTS because of high rate of restenosis. Experience in using HDR brachytherapy to prevent restenosis in two cases of BCTS is reported. CASES REPORT: There were two cases of BCTS who received HDR brachytherapy in order to prevent restenosis. First case was a 39 year-old female who had 5 cms tracheal and 2 cms left main bronchial stenosis from previous endobronchial tuberculosis. After 36 procedures of tracheobronchial dilatation by rigid bronchoscopy and two tracheal stents placement, her trachea became restenosis in an average time of 1 month. She also developed anaphylactic reaction with lidocaine. She received HDR brachytherapy with the dose of 10 Gy and no restenosis was found after 5 months follow-up. The second case was a 18 year-old male who had 4 cms tracheal stenosis result from post intubation. He was done dilatation and stenting of the trachea by regid bronchoscopy because he refused surgery. After 1 year the tracheal stent was removed and rapid restenosis of the trachea resulted in respiratory failure occurred in 7 days. The tracheal stent was reimplanted and 1 year later 7.0 Gy HDR brachytherapy was done after stent removal. He was doing well 4 months after with 50% tracheal stenosis and occasional stridor. CONCLUSION: Failure of intervention bronchoscopic techniques in management of BCTS was significantly shown by the restenosis even after endobronchial stent placement. HDR brachytherapy had a beneficial role in preventing granulation tissue formation and delay or prevent restenosis after bronchoscopic dilatation in selected case of BCTS patients. The case selection and long term outcome were needed before introduced HDR brachytherapy to be the standard care of BCTS patients.

Impact of endobroncial ultrasound guided transbrocnhial needle aspiration on clinical practice guideline.

OBJECTIVE: Endobronchial ultrasound guided transbronchial needle aspiration (EBUS TBNA) is performed by using special bronchoscope which has an ultrasound probe at its tip that could demonstrate lymph node outside the airway and allow for real time observation of transbronchial needle aspiration. The sensitivity and specificity of EBUS TBNA are high in many studies. However because of the high expense and special training required, the impact of this method on clinical practice guidelines (CPG) needs to be further evaluated. MATERIAL AND METHOD: The patients were classified to three groups. Group One included proven lung cancer patients who do not have distant metastasis and no mediastinal lymphadenopathy as demonstrated by computer tomography. Group Two was the same as group One except there was evidence of mediastinal lymphadenopathy. The Third Group included patients who only had mediastinal lymphadenopathy without lung lesion. All lymph node stations were examined by EBUS and their sizes were recorded. Selected puncture of a lymph node was done and tissue was sent for cytological examination. There was no rapid on site cytologic examination. The impact on CPG was calculated from the number of patients who be prevented from mediastinoacopy. RESULTS: There were 158 patients in the present study. The number of patients in group 1, 2 and 3 were 64, 57 and 37 respectively. The mean size of the mediastinal lymph node which detected by EBUS was 1.34 cm (range 0.36-3.81 cm). TBNAs were done in 164 nodes out of 353 nodes found by EBUS. The most common enlarged mediastinal node was at station 7 and those at station 4R and 3 were less common in sequence. In all three groups, malignant cells were established in 71 patients (44.9%). In group 1 malignancy was found in 21 (32.8%), in 39 patients (68.4%) in group 2 and in 11 patients (29.7%) in group 3. DISCUSSION: If the CPG recommend mediastinoscopy for all lung cancer patients, EBUS TBNA can save 49.5% of patients from the procedure. But if only enlarged mediastinal node would be considered for mediastinoscopy, EBUS TBNA can save up to 59.5% patients from mediastinal surgery. CONCLUSION: EBUS TBNA has impact on CPG for assessment of mediastinal node in lung cancer and mediastinal lymphadenopathy patients.

The endobronchial ultrasound-guided transbronchial lung biopsy in peripheral pulmonary lesions.

BACKGROUND: Peripheral pulmonary lesions are technically challenging with conventional bronchoscopy in obtaining tissue diagnosis. The recently developed small-caliber ultrasonographic probe can be introduced via the working channel of a flexible bronchoscope to localize peripheral pulmonary lesions (PPLs) prior to transbronchial lung biopsy (TBLB). The endobronchial ultrasound-guided transbronchial lung biopsy (EBUS-TBLB) is a new diagnostic method for the diagnosis of pulmonary lesions in our center. OBJECTIVE: To evaluate the diagnostic yield of EBUS-TBLB in pulmonary lesions. STUDY DESIGN: A prospective cross-sectional study. MATERIAL AND METHOD: We enrolled 152 patients with pulmonary lesions that were beyond the segmental bronchus and had no evidence of endobronchial lesion, who underwent bronchoscopy in our center. With EBUS assisted, transbronchial lung biopsy was performed after localizing and measuring distance from the tip of bronchoscope to the lesion. The diagnostic yield was calculated. RESULTS: The pulmonary lesions were visible on EBUS image in 98.7% of cases. The overall diagnostic yield of EBUS-TBLB was 66.4%. The diagnostic yield in the infiltrative and mass lesions were 86.4% and 63.1%, respectively. The lesions which EBUS probe located within it were diagnosed by EBUS-TBLB about 74.8%. The benign and malignant lesions were diagnosed by EBUS-TBLB about 81.1% and 58.6%, respectively. The average EBUS time was 3.55 +/- 2.29 minutes. No complication of EBUS and transbronchial lung biopsy were observed in this study. CONCLUSION: EBUS-TBLB is a safe procedure for diagnosing pulmonary lesions. Our results indicate that the EBUS-TBLB improves the diagnostic yield compared to conventional brochoscopy.