Bronchitis Medical and Health News Headlines

Bronchiolitis obliterans syndrome: alloimmune-dependent and -independent injury with aberrant tissue remodeling.

Semin Thorac Cardiovasc Surg. 2008;20(2):173-82

Authors: Sato M, Keshavjee S

Long-term success in lung transplantation continues to be challenged by chronic graft dysfunction, which is manifest as bronchiolitis obliterans syndrome (BOS). The mechanisms of BOS involve both immune-mediated pathways (rejection, autoimmune-like mechanisms), and alloimmune-independent pathways (infection, aspiration, ischemia, primary graft failure), which lead to a fibroproliferative responses. BOS correlates histologically with obliterative bronchiolitis in terminal bronchioles and evidence of aberrant remodeling in the airway epithelium, vasculature, stroma, and lymphoid system. A potentially important mechanism that supports the progressive and therapy-resistant nature of BOS is a continuous cycle of ongoing injury and aberrant remodeling. Namely, anatomical and functional abnormalities induce and exacerbate immune-mediated and alloimmune-independent pathways through various mechanisms (e.g., epithelial remodeling decreases mucociliary clearance that exacerbates aspiration-related injury). From this viewpoint, we review current therapeutic strategies and revisit the role of transplant surgeons in attenuating the initial transplant-related injuries to prevent the lung grafts from entering the remodeling-injury cycle.

PMID: 18707652 [PubMed - in process]

Diacetyl and bronchiolitis obliterans.

Am J Respir Crit Care Med. 2008 Aug 1;178(3):313; author reply 313-4

Authors: Galbraith DA, Weill D

PMID: 18650571 [PubMed - in process]

Human Metapneumovirus in Lung Transplant Recipients and Comparison to Respiratory Syncitial Virus.

Am J Respir Crit Care Med. 2008 Jul 24;

Authors: Hopkins P, McNeil K, Kermeen F, Musk M, McQueen E, Mackay I, Sloots T, Nissen M

RATIONALE: Human Metapneumovirus is a newly described virus isolated in 2001 from children with acute respiratory infection. It has subsequently been reported globally although there is limited data in lung transplant recipients. OBJECTIVES: 1) To prospectively analyse whether human Metapneumovirus was circulating in our adult lung transplant community and assess the morbidity of this infection 2) Compare to respiratory syncytial virus, the clinical presentation and outcome following intravenous ribavirin. METHODS: Lung transplant patients with clinical features of respiratory viral infection underwent nasopharyngeal aspirates. Patients with a positive specimen for either respiratory syncytial virus or human Metapneumovirus by reverse transcriptase PCR analysis and graft dysfunction received intravenous ribavirin and pulse steroid therapy. MAIN RESULTS: Eighty-nine patients had 199 visits for aspirate studies. A viral cause was determined for 62 visits in 47 patients (19 human Metapneumovirus, 18 respiratory syncytial virus, 13 parainfluenza, 9 influenza A, 2 adenovirus and 1 influenza B). A significant percentage of Metapneumovirus (63%) and respiratory syncytial virus (72%) patients developed graft dysfunction with average decline in FEV1 of 30+/-12.4% and 25.9+/-11.2% respectively. In these patients, bronchiolitis obliterans syndrome onset or progression occurred in no patients with human Metapneumovirus compared with 5 of 13 (38%) respiratory syncytial virus patients at 6 months. CONCLUSIONS: Human Metapneumovirus is a leading cause of acute respiratory tract illness in lung transplant recipients. The incidence and clinical spectrum at presentation are similar to respiratory syncytial virus although the latter does appear to be associated with a higher risk of chronic rejection. We recommend testing for human Metapneumovirus to assess local epidemiological patterns.

PMID: 18658110 [PubMed - as supplied by publisher]

Th1 and Th2 cytokine levels in nasopharyngeal aspirates from children with human bocavirus bronchiolitis.

J Clin Virol. 2008 Jul 21;

Authors: Chung JY, Han TH, Kim JS, Kim SW, Park CG, Hwang ES

BACKGROUND: Human bocavirus (hBoV) is regarded as one of the possible etiologic agents in lower respiratory tract infection and bronchial asthma exacerbation in children despite frequent co-detection with other respiratory viruses. The immunologic response in children with hBoV infection is still not clear. OBJECTIVES: To investigate the profiles of T helper-1 (Th1)/T helper-2 (Th2) cytokines in children with hBoV-associated bronchiolitis. STUDY DESIGN: This study utilized of 59 nasopharyngeal aspirates from 59 infants aged 24 months or younger, including 29 from children with hBoV-related bronchiolitis and 30 with respiratory syncytial virus (RSV)-related bronchiolitis. Eighteen infants hospitalized for elective surgeries were included as controls. Nasopharyngeal aspirates were tested simultaneously for cytokines interleukin (IL)-2, IL-4, IL-5, IL-10, interferon (IFN)-gamma, and tumor necrosis factor (TNF)-alpha using the Cytometric Bead Array. RESULTS: Significantly higher concentrations of IFN-gamma (p=0.0001), IL-2 (0.006), and IL-4 (p=0.0002) were observed in hBoV positive specimens than in controls. The concentration of IL-10 (p=0.04) and TNF-alpha (p=0.006) in the RSV-positive group was significantly higher than in the hBoV-positive group, while there was no difference in other cytokines concentration between the two groups. CONCLUSIONS: These results showed that both of Th1 and Th2 cytokines were increased in children with hBoV-related bronchiolitis compared to normal controls, but Th2-polarized responses were not observed.

PMID: 18650126 [PubMed - as supplied by publisher]

CD28 Downregulation on CD4 T-Cells is a Marker for Graft Dysfunction in Lung Transplant Recipients.

Am J Respir Crit Care Med. 2008 Jul 10;

Authors: Studer SM, George MP, Zhu X, Song Y, Valentine VG, Stoner MW, Sethi J, Steele C, Duncan SR

RATIONALE: Repeated antigen-driven proliferations cause CD28 on T-cells to downregulate. We hypothesized alloantigen-induced proliferations could cause CD28 downregulation in lung transplant recipients. OBJECTIVES: To ascertain if CD28 downregulation on CD4 T-cells associated with manifestations of allograft dysfunction in lung transplant recipients. METHODS: Peripheral blood CD4 T-cells from 65 recipients were analyzed by flow cytometry, cytokine multiplex and proliferative assays, and correlated with clinical events. MEASUREMENTS AND MAIN RESULTS: Findings that CD28 was present on <90% of total CD4 T-cells were predominantly seen among the recipients with bronchiolitis obliterans syndrome (specificity=88%). Perforin and granzyme B were produced by >50% of the CD4(+)CD28(null) cells, but <6% of autologous CD4(+)CD28(+) cells (p</=0.006). CD4(+)CD28(null) cells also had increased productions of proinflammatory cytokines, but less frequently expressed regulatory T-cell marker FoxP3 (2.1+/-1.3%), compared to autologous CD4(+)CD28(+) (9.5+/-1.4, p=0.01). Cyclosporine A (100 ng/ml) inhibited proliferation of CD4(+)CD28(null) cells by 33+/-11% vs. 68+/-12% inhibition of CD4(+)CD28(null) (p=0.025). FEV1 fell six months later (0.35+/-0.04L) in recipients with CD4(+)CD28(+)/CD4total<90% (CD28% Low) compared to 0.08+/-0.08L among CD4(+)CD28(+)/CD4total>90% (CD28% High) recipients (p=0.013). Two-year freedom from death or retransplantation in CD28% Low recipients was 32+/-10%, vs. 78+/-6% among the CD28% High subjects (p<0.0001). CONCLUSIONS: CD28 downregulation on CD4 cells is associated with bronchiolitis obliterans syndrome and poor outcomes in lung transplantation recipients. CD4(+)CD28(null) cells could be important in the progression of allograft dysfunction. These findings may illuminate a novel paradigm of transplantation immunopathogenesis, and suggest CD28 measurements could identify recipients at risk for clinical deteriorations.

PMID: 18617642 [PubMed - as supplied by publisher]