Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0032285 (pneumonia)
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The aim of the present study was to further characterize the role of alveolar macrophages (AM) in acute human lung inflammation by evaluating their capacity to produce pro-inflammatory cytokines such as tumour necrosis factor (TNF)-alpha, interleukin (IL)-6 and IL-8. Patients with severe community-acquired pneumonia (CAP; n=12) and healthy volunteers (n=10) underwent bronchoalveolar lavage (BAL). AM were separated to high purity (>96%) using fluorescence-activated cell sorting. We determined the TNF-alpha, IL-6 and IL-8 cytokine gene expression in AM ex vivo using semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR). Moreover, we measured in vitro unstimulated, lipopolysaccharide (LPS)- and LPS/interferon-gamma inducible TNF-alpha, IL-6 and IL-8 cytokine release and evaluated samples of BAL fluids for the same pro-inflammatory cytokines using an enzyme-linked immunosorbent assay (ELISA). We found increased TNF-alpha, IL-6 and IL-8 messenger ribonucleic acid (mRNA) levels in AM from CAP patients that were significantly elevated only for IL-8. When challenged with endotoxin in vitro, AM obtained from CAP patients showed a strongly reduced potential to release TNF-alpha and IL-6 compared to healthy controls, whereas IL-8 secretion did not differ significantly between groups. Moreover, stimulation of AM from CAP patients with LPS plus IFN-gamma augmented TNF-alpha and IL-6 cytokine release to near normal levels. Interestingly, no TNF-alpha protein was measured in BAL samples from CAP patients, whereas IL-6 and IL-8 protein levels were found to be significantly increased. Together, highly purified alveolar macrophages from community-acquired pneumonia patients show relatively low ex vivo tumour necrosis factor-alpha and interleukin-6 but not interleukin-8 messenger ribonucleic acid levels that are associated with a decreased pro-inflammatory cytokine release in vitro which, however, can be restored by concurrent interferon-gamma stimulation.
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PMID:Expression of pro-inflammatory cytokines by flow-sorted alveolar macrophages in severe pneumonia. 959 98

We identified all patients under the age of 65 dying from CAP over a 3-yr-period in hospital in our health district. Most had chronic underlying illnesses. The early management of those who had previously been in good health was studied in greater detail, and was not ideal. Recommendations have been made to try and improve the assessment and treatment of patients with severe community-acquired pneumonia.
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PMID:Early management of younger adults dying of community acquired pneumonia. 972 29

We suggest the following strategy for managing patients with pneumonia. For nonventilated patients with either CAP or HAP, empiric antibiotic treatment should be started according to approved guidelines, and if the clinical evolution of the patient is not adequate, fiberoptic bronchoscopy including PSB and BAL could be considered, with modification of the antibiotic treatment accordingly. In ventilated patients with either CAP or HAP, respiratory secretion sampling using noninvasive techniques should be conducted upon clinical suspicion of VAP and before starting a new antibiotic treatment. Antibiotic therapy according to approved guidelines should be started as soon as possible and maintained during the first 48 hours if the patient's evolution is satisfactory and condition has stabilized. Then, initial antibiotic treatment should be adjusted according to cultures. If there is a clear diagnostic alternative to VAP and cultures are negative, this is the only case in which antibiotic treatment could be withdrawn. If the patient's clinical evolution is inadequate (persistence of fever, leukocytosis, increasing infiltrates, and respiratory failure), fiberoptic bronchoscopy with PSB and BAL and modification of the initial antibiotic regimen should be sought. Open lung biopsy may be indicated in patients with diffuse pulmonary infiltrates in whom a diagnosis has not been achieved by other methods, including bronchoscopy. Transbronchial lung biopsy should not be viewed as a diagnostic technique for pneumonia except in immunosuppressed patients with diffuse alveolar infiltrates.
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PMID:Invasive diagnostic techniques for pneumonia: protected specimen brush, bronchoalveolar lavage, and lung biopsy methods. 977 86

Community-acquired pneumonia is a common and severe illness. S. pneumoniae remains the most common cause of CAP; however, more than 100 microbials cause this illness. Antibiotic treatment is dictated by the severity of the pneumonia.
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PMID:Community-acquired pneumonia: epidemiology, etiology, treatment. 977 87

Rapidly burgeoning worldwide multiple drug-resistant pneumococcal serotypes pose an urgent demand for new management approaches. Perhaps modern intensive care methods may have alternatives to offer. Indeed, standard assessments such as the admission APACHE II score may overestimate individual risk of death in severe CAP, and mortality can be reduced. However, among those at highest risk for mortality in the early phase of invasive disease, the conclusions reached 2-3 decades ago, that it is questionable whether a more effective drug than penicillin can be developed, and that a reduction in the number of deaths consequent to this infection can be accomplished only by widespread immunoprophylactic measures, remain inescapable. Clearly, as discussed elsewhere in this supplement, the continuing validity of these 20-year-old conclusions and the global prevalence of DRSP demand the development and marketing of new conjugate vaccines, although more widespread use of the existing 23-valent polysaccharide vaccine among high-risk populations is essential in the interim. With respect to resistance selection pressures, antibiotic prescription control may provide the answer. However, patient expectations of antibiotic therapy for trivial respiratory infection is high and, in the United Kingdom, 75% of previously healthy adults will receive it; those who do not will usually consult another physician in an effort to secure such therapy. Thus, without the intervention of government or managed care organizations, self-regulation in prescribing is unlikely. The evidence for beta-lactam treatment failure in meningitis has led to alternative approaches, with vancomycin as the primary agent. Penicillins may remain effective for otitis media, but oral cephalosporins are suspect. Data on pediatric pneumococcal pneumonia continue to suggest use of beta-lactams, at least for disease caused by strains with intermediate penicillin sensitivity. Pallares et al concluded that penicillins and cephalosporins remain the drugs of choice for severe pneumococcal pneumonia in adults. Others who share this conclusion often cite that study as evidence. However, in the case of penicillins, the mortality rate was 6% higher in a subgroup selected for monomicrobial infection and reduced risk factors for mortality when penicillin-resistant infection was present, and the overall mortality was 14% higher with penicillin-resistant strains (taking into account "all comers"). Those who depend on the findings of evidence-based medicine may accept the premise that penicillins and cephalosporins remain the drugs of choice, and agree with Goldstein and Garau that it would indeed be a mistake to adopt alternative therapies. Others may consider the deaths of 6 of 100 patients who were not in the highest-risk group too high a price to pay for statistical significance and may be skeptical of the continued use of beta-lactam therapy on higher-risk patients. In addition, the persistent selection pressure applied by continued use of beta-lactams offers a powerful population-based argument for alternatives. As DRSP continues to spread and resistant strains with penicillin MIC >2 mg/L become more prevalent, new agents such as the azabicyclo-methoxyquinolone, moxifloxacin, and perhaps grepafloxacin, but not the more toxic sparfloxacin and trovafloxacin, will undoubtedly flourish as treatments for CAP. By that time, the results of clinical studies on ketolides and oxazolidinones could offer further choices.
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PMID:Therapy for pneumococcal infection at the millennium: doubts and certainties. 1045 Oct 13

Severe CAP is a life-threatening condition defined by the presence of respiratory failure or symptoms of severe sepsis or septic shock. It accounts for approximately 10% of hospitalized patients with CAP. The majority of patients with severe pneumonia have underlying comorbid illnesses, with COPD, alcoholism, chronic heart disease, and diabetes mellitus being the most frequent. S. pneumoniae, Legionella spp, GNEB (especially K. pneumoniae), H. influenzae, S. aureus/spp, Mycoplasma pneumoniae, respiratory viruses (especially influenza viruses), and P. aeruginosa represent the most important causative organisms of severe CAP. Rapid initiation of appropriate antimicrobial treatment is crucial for a favorable outcome. Initial antimicrobial treatment should be based on an epidemiological (empiric) approach. Microbial investigation may be helpful in the individual case but is probably more useful to define local antimicrobial policies based on local epidemiologic and susceptibility patterns. Mortality rates range from 21% to 54%. The most important prognostic factors include general health state of the patient, appropriateness of initial antimicrobial treatment, and the existence of bacteremia, as well as factors reflecting severe respiratory failure, severe sepsis, septic hypotension or shock, and the extent of infiltrates in chest radiograph. Initial antimicrobial treatment should consist of a second (or third) generation cephalosporin and erythromycin. Modifications of this basic regimen should be considered in the presence of distinct comorbid conditions and risk factors for distinct pathogens. Promising new approaches of nonantimicrobial treatment, including noninvasive ventilation, treatment of hypoxemia, and immunomodulation, are under investigation.
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PMID:Severe community-acquired pneumonia. 1051 5

The treatment of the hospitalized patient with uncomplicated CAP is changing, to include a brief period of intravenous antibiotics followed by oral therapy. The Classification of Community-Acquired Pneumonia or CoCAP is a stratification tool that categorizes patients as low-risk pneumonia, unstable pneumonia, or complicated pneumonia. Use of validated hospital admission criteria, combined with the CoCAP algorithm and evolving criteria for switching patients from intravenous to oral therapy provides a structure for organizing treatment of patients with CAP for caregivers. Patients who can be discharged early are those from the unstable pneumonia group, which includes patients who have had reversal of their metabolic problems and stabilization of comorbid conditions, and who have not developed any serious pneumonia-related complications. Prolonged courses of intravenous antibiotic therapy are being replaced with 2 to 3 day courses of intravenous hydration and antibiotics; a switch to oral therapy and hospital discharge can be achieved after the patient tolerates one dose of oral therapy. Parameters to watch include vital signs and white blood cell count. Provided these parameters are improving, although they may not have returned to normal, the patient can be switched to oral therapy. Although patient treatment guidelines and critical pathways are becoming widespread in disease management, CAP is one disease in which prospective studies have demonstrated that a reduction in hospital stay is safe. Patients, caregivers, and administrators are happy with the reduction in hospital LOS. Other treatment protocols are being explored, including a single dose of intravenous antibiotic prior to oral switch and all-oral regimens employing the newer fluoroquinolones.
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PMID:Strategies for early discharge of the hospitalized patient with community-acquired pneumonia. 1051 7

Given the variability in rate of radiographic resolution, it remains controversial to decide when to initiate an invasive diagnostic work-up for nonresolving or slowly resolving pulmonary infiltrates. In immunocompetent patients who present with classical features of CAP (i.e., fever, chills, productive cough, new pulmonary infiltrate), clinical response to therapy is the most important determinant for further diagnostic studies. Within the first few days, persistence or even progression of infiltrates on chest radiographs is not unusual. Defervescence, diminished symptoms, and resolution of leukocytosis strongly support a response to antibiotic therapy, even when chest radiographic abnormalities persist. In this context, observation alone is reasonable, and invasive procedures can be deferred. Serial radiographs and clinical examinations dictate subsequent evaluation. In contrast, when clinical improvement has not occurred and chest radiographs are unchanged or worse, a more aggressive approach is warranted. In this setting, we advise fiberoptic bronchoscopy with BAL and appropriate cultures for bacteria, legionella, fungi, and mycobacteria. When endobronchial anatomy is normal and there is no purulence to suggest infection, TBBs should be done to exclude noninfectious causes (discussed earlier) or infections attributable to mycobacteria or fungi. An aggressive approach is also warranted in patients who are clinically stable or improving when the rate of radiographic resolution is delayed. As discussed earlier, what constitutes excessive delay is controversial, and depends upon the acuity of illness, specific pathogen, extent of involvement (i.e., lobar versus multilobar), comorbidities, and diverse host factors. Stable infiltrates even 2 to 4 weeks after institution of antibiotic therapy does not mandate intervention provided patients are improving clinically. Invasive techniques can also be deferred when unequivocal, albeit incomplete, radiographic resolution can be demonstrated. Lack of at least partial radiographic resolution by 6 weeks, even in asymptomatic patients, however, deserves consideration of alternative causes (e.g., endobronchial obstructing lesions, or noninfectious causes). Fiberoptic bronchoscopy with BAL and TBBs has minimal morbidity and is the preferred initial invasive procedure for detecting endobronchial lesions or substantiating noninfectious causes. The yield of bronchoscopy depends on demographics, radiographic features, and pre-test likelihood. In the absence of specific risk factors, the incidence of obstructing lesions (e.g., bronchogenic carcinomas, bronchial adenomas, obstructive foreign body) is low. Bronchogenic carcinoma is rare in nonsmoking, young (< 50 years) patients but is a legitimate consideration in older patients with a history of tobacco abuse. Non-neoplastic causes (e.g., pulmonary vasculitis, hypersensitivity pneumonia, etc.) should be considered when specific features are present (e.g., hematuria, appropriate epidemiologic exposures). Ancillary serologic tests or biopsies of extrapulmonary sites are invaluable in some cases. In rare instances, surgical (open or VATS) biopsy is necessary to diagnose refractory or non-resolving "pneumonias."
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PMID:Nonresolving or slowly resolving pneumonia. 1051 9

Bedside fiberoptic bronchoscopy is a valuable tool in the diagnosis and treatment of various respiratory conditions in critically ill patients. The fiberoptic bronchoscope allows direct airway inspection, facilitating the diagnosis of benign and malignant airway lesions. In addition, pulmonary secretions or tissue samples can be collected using the bronchoscope and techniques that allow sampling of the lower airways with minimal or no upper airway contamination. Collection of lower airway samples is important in the diagnosis of pulmonary infiltrates in immunocompromised patients, in many patients with ventilator-associated pneumonia, and in selected patients with CAP. The fiberoptic bronchoscope can be used for therapeutic interventions, such as insertion of an endotracheal tube, removal of an aspirated foreign body, clearance of tenacious secretions, promotion of hemostasis in patients with hemoptysis, instillation of drugs, and assistance in the placement of tracheobronchial prostheses (i.e., airway stents). If proper preprocedural training and planning are done and the patient is monitored carefully during the procedure, fiberoptic bronchoscopy can be performed quickly and safely at the bedside in most critically ill patients.
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PMID:Fiberoptic bronchoscopy for diagnosis and treatment. 1065 May 1

The etiologic agents in 200 patients with pneumonia were studied by the bacterial culture of sputums obtained from the protected single catheter brush or quantitative expectoration at one morning or three-morning expectoration. Two hundred patients were divided into 3 groups. Group 1 was Nosocomial pneumonia (NP patients). Group 2-1 and Group 2-2 were community acquired pneumonia (CAP patients). All cases in Group 1 and Group 2-2 suffered from significant underlying diseases while Group 2-1 did not. Gram-negative bacilli(GNB) were isolated from the specimens in Group 1 (87%) and Group 2-2 (75%), respectively. Pseudomonas (30.8%) and klebsiella (20.5%) were the predominant bacteria (in Group 1 and pseudomonas bacteria) in Group 1 and pseudomonas (27.3%), acinetobacter (23%) and kledsiella (18%) were the major etiologic agents in Group 2-2. The commonest pathogens in Group 2-1 were gram-positive cocci (75%), in which streptococcus (38%) and staphylococcus aureus (25%) were the dominant agents. Compared with Group 2, Group 1 suffered from more mixed bacteria and the agents presented severer drug-resistant. The prognosis was worse in Group 2-2 than in Group 2-1. The results showed that the GNB pneumonia was more common in the cases who had underlying disease, no matter whether the pneumonia was NP or CAP. These patients had more trouble on their antibiotic therapy. Thus it is important that doctors should use vigorous antibiotics timely while treating these patients' underying diseases.
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PMID:[A prospective study on etiologic bacteria in 200 patients with pneumonia]. 1068 59


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