HOMO SAPIENS DISEASES - RESPIRATORY APPARATUS

Table of contents :


Examinations Respiratory apparatus diseases
  • Diseases of the mediastinum
  • Diseases of thoracic cage 
  • Acute thoracic pain
  • Web resources 
  • Bibliography

  • Symptoms :

    Signs Laboratory examinations Respiratory apparatus diseases The community-acquired respiratory viruses (CRVs) are well known for their ability to cause misery during the winter cold and flu season. CRVs such as the influenza viruses, parainfluenza viruses, and respiratory syncytial virus (RSV), however, may be fatal for patients with hematologic malignancies, particularly those who are recipients of allogeneic hematopoietic cell transplantation (HCT). Though most clinicians believe that mortality after incident CRV infection is chiefly mediated via viral pneumonitis and acute pulmonary failure, accumulating data suggest that even upper respiratory tract infections (URIs) with some of these viruses may be associated with increased long-term mortality after HCT. Moreover, the application of PCR-based diagnostics now allows a wider variety of potential pathogens to be identified, including those that are difficult to cultivate (e.g., human rhinoviruses and coronaviruses) and/or newly discovered (e.g., human metapneumovirus [hMPV]). Thus, it is likely that the full spectrum of disease associated with these potent pathogens remains to be elucidated.
    Epidemiology : the CRVs are ubiquitous; otherwise healthy individuals typically experience 2–6 URIs with these viruses per year, with higher attack rates associated with younger age. Though the CRVs are capable of causing pneumonia even in the immunocompetent host (particularly those who are at extremes of age), they are better known for their role in the common cold and other related clinical syndromes, including pharyngitis, tracheobronchitis, and bronchiolitis. Among patients with hematologic malignancies, however, CRV infection may result in interstitial pneumonia and is now more likely to be found than cytomegalovirus (CMV) in patients with pneumonia early after HCT. Studies conducted at the Fred Hutchinson Cancer Research Center (FHCRC), the MD Anderson Cancer Center, and elsewhere have shown that the epidemiology of CRV infections closely parallels the occurrence of these infections in the community, such that RSV and influenza infections most commonly occur during the well-defined winter and early spring "flu season"; infections due to parainfluenza viruses (PIVs), however, appear to occur year-roundref1, ref2, ref3, ref4. The CRVs are also notable for their propensity to spread nosocomially to other patients and healthcare workers. Thus, the occurrence of CRV infection is distinct from the pattern seen with endogenous human herpesviruses, where reactivation knows no season and appears to be primarily correlated with either GVHD and/or the net state of immunosuppression. Reported rates of respiratory virus infections among HCT recipients have varied widely over time depending on the patient population, transplantation regimen, and type of surveillance institutedref1, ref2, ref3, ref4. Prospective, culture-based surveillance carried out at MD Anderson Cancer Center in the 1990s showed that approximately one-third of patients with upper respiratory tract symptoms (nasal congestion, cough, or sore throat) were infected with community-acquired respiratory viruses such as RSV, PIV, adenovirus, or influenzaref. Longitudinal studies carried out at FHCRC over the past decade have reported rates of CRV infection between 5% and 10% during the early period after transplantationref, with more recent studies describing overall virus-specific rates of 5%, 7%, and 1%–2% for RSV, parainfluenza and influenza virus, respectively, during the first 100 days after transplantationref1, ref2 (Nichols WG, Guthrie KA, Corey L, Boeckh M. Influenza infections after stem cell transplantation: risk factors, mortality and the effect of antiviral therapy. Biol Blood Marrow Transplant. 2003;9:73–74). These studies likely still underestimate the true incidence of CRV infections in this population. This is because testing has been traditionally applied only to the most symptomatic inpatients rather than to all HCT recipients, and culture-based testing strategies lack sensitivity for the diagnosis of respiratory viral infections. Highly sensitive real-time quantitative reverse transcriptase PCR (RT-PCR) assays have now been developed that permit the detection of even more cases of RSV, PIV, and influenza virus infections than previously possible. van Elden et al investigated the use of RT-PCR to identify CRVs in stored bronchoalveolar lavage (BAL) and nasal wash samples that had been obtained from patients with hematological malignancies and pneumonia, and found that diagnostic yield increased from 19% to 35% in this settingref; in a separate study, PCR-based detection tripled the detection rate for RSV among immunocompromised adultsref. PCR also offers the ability to detect viruses that have heretofore been difficult to isolate in culture (including hMPV, the rhinoviruses, and the coronaviruses), and potentially offers the ability to target therapy according to quantitative virologic cutpoints. Together, these studies indicate a need for re-evaluation of the importance of the CRVs in patients with hematologic malignancies using modern diagnostic assays.
    Impact of CRV infections : Impact of "uncultivated" viruses : hMPV is a newly discovered human respiratory virus that may be associated with as many as 10%–25% of cases of viral upper and lower respiratory tract disease in children. Like RSV, lower respiratory tract disease appears to develop primarily in the very young and the very old, although the rate of hMPV-related pneumonia in previously healthy young children appears to be lower than that associated with either RSV or influenza infection. Clinical features are virtually indistinguishable from those associated with RSV, though wheezing may be more common with the latter. More serious disease has been associated with hMPV infection in immunocompromised patients, with fatalities reported in at least 2 cases—1 child with leukemiaref and 1 adult who underwent bone marrow transplantationref. We have recently detected hMPV in cryopreserved BAL fluid of 5 HCT recipients who expired with pulmonary failure; diagnosis for 4 of these patients at death was "idiopathic pneumonia syndrome" or "diffuse alveolar hemorrhage" (Englund J, Nichols WG, et al, submitted for publication). hMPV may thus be responsible for at least a proportion of cases of idiopathic pneumonia syndrome after HCT; the full spectrum of disease caused by this virus has yet to be determined. Rhinovirus and coronaviruses circulate widely and are believed to be the most common causes of the common cold in the immunocompetent host. Their association with severe respiratory disease in the patient with hematologic malignancy, however, is controversial. Investigators from the MD Anderson Cancer Center have reported that rhinovirus may cause lower tract disease by itselfref, though 2 separate analyses from our centerref1, ref2 did not provide conclusive evidence for rhinovirus pneumonia in HCT recipients. In the most recent study, 77 BAL samples obtained from HCT recipients with pneumonia were screened with sensitive RT-PCR assays; though 8 were positive for rhinovirus RNA and mortality was high in these patients, all had significant copathogens presentref. The contribution of the human coronaviruses to respiratory disease in this patient population is more obscure. In 2 recent studies that examined cryopreserved BAL fluid obtained from patients after HCT or with underlying hematologic malignancies, coronaviruses were found only rarely (1 of 43 specimens)ref or not at all (0 of 46 specimens)ref. Milder disease and/or long-term pulmonary complications associated with these viruses, however, need to be ruled out with prospective studies.
    Therapy : as discussed above, the direct mortality associated with CRV infections appears to have decreased over the past decade. While newer antivirals may be responsible for some of the improved outcomes, it is more likely that the earlier application of antivirals that have long been available (such as aerosolized ribavirin) accounts for improved outcomes for many infections, including RSVref. Rapid identification of the infecting virus (i.e., with BAL) is necessary to allow prompt therapy, since mortality is high if pulmonary failure is present when antiviral therapy is applied. BAL is also crucial to identify the significant copathogens that are frequently present in these patients, which require additive therapy for optimal outcome. Prevention : stringent infection control practices are critical for decreasing the morbidity and mortality associated with incident CRV infection in the at-risk host. Focus should first be directed toward the prevention of nosocomial infections during the period of highest risk (i.e., during the periods of profound lymphopenia that follow conditioning or induction chemotherapy, when progression to pneumonia appears most likely). Incident infections still may occur later after patients have returned to the community, but these are associated with lower direct mortality. Since large droplets are the most important means of viral transmission, frequent handwashing (or use of alcohol-based hand sanitizers) cannot be overemphasized; targets for this teaching include healthcare workers, close patient contacts, and the patients themselves. Recommendations for screening and isolation of patients with CRV infections have been summarized by the Centers for Disease Control and Prevention (CDC) and the American Society for Blood and Marrow Transplantation (ASBMT)ref. HCT recipients and those at high risk for CRV-related complications should refrain from contact with individuals with symptomatic CRV infections; symptomatic healthcare workers or visitors should thus be restricted from access to wards where these patients are housed. Whether masks for patients or asymptomatic healthcare workers (prior to patient contact) add value to hand hygiene and the restrictions above is debatable. Inactivated influenza vaccine is an effective means to prevent this important CRV infection and should be offered yearly to nearly all patients with hematologic malignancies (patients in their first year after transplant are the possible exception due to poor antibody responses). Healthcare workers and close patient contacts should also receive the inactivated vaccine to reduce transmission to patients. Live attenuated influenza vaccine cannot currently be recommended for patients or their close contacts (including healthcare workers) due to concerns of vaccine strain transmission and resulting clinical illness in these immunocompromised hosts.

    Acute chest pain :
    Aetiology :

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