It is extremely difficult to draw definitive conclusions about the effectiveness of the aforementioned interventions for the treatment of BO. The majority of reports consist of anecdotal, single-center, nonrandomized, and uncontrolled investigations with relatively small sample sizes. In addition, it appears that most reports indicate stabilization or slowing of the rate of loss of lung function. It is unclear whether this represents a therapeutic benefit or simply the natural history of BO in these subjects. Read the rest of this entry »
Other immune-modulating treatment strategies used against BO include extracorporeal photochemotherapy, plasmapheresis, total lymphoid irradiation, and allogeneic bone marrow transplantation to achieve chimerism. To date, the numbers of patients treated with these strategies are too small to be conclusive. Extracorporeal photochemotherapy has been approved for use in cutaneous T-cell lymphoma and appears to be effective for this indication. Extracorporeal photochemotherapy has been used on an experimental basis for solid organ transplant rejection, although the mechanism of action is not fully understood. Animal models suggest that there might be a vaccination effect of photomodulated cells against pathogenic T-cell clones. A small study in three patients with BO showed stabilization of lung function for at least 6 to 23 months in all of the patients. Two other reports described stabilization or improvement of FEVj^ in five of nine patients and four of six patients with BO, respectively. Read the rest of this entry »
Inhaled Immunosuppressive Drugs
Targeted delivery of immunosuppressive agents directed to the graft has been applied in experimental systems for years. The rationale for targeted delivery was to achieve higher local levels of the drug with less systemic toxicity. Additionally, it has been hypothesized that the drug may act along pathways not accessible from the systemic route alone.
In an experimental lung transplant model, bronchial mucosal blood flow was documented to be decreased markedly during acute rejection episodes. It is therefore possible that alterations in blood flow may occur in chronic lung rejection. Hence, inhalation of immunosuppressive agents could potentially have effects beyond what would be expected with systemic delivery alone. Read the rest of this entry »
Tacrolimus as a substitute for cyclosporine was shown anecdotally to stabilize the course of two patients with BO. A large randomized trial of 133 patients compared tacrolimus to cyclosporine as first-line immunosuppressive therapy. Patients receiving tacrolimus had fewer acute rejection episodes per 100 patient-days (0.85±0.72) compared with the patients given cyclosporine (1.09 ±0.72), although the difference did not reach significance (p=0.07). Significantly fewer patients given tacrolimus developed BO (13 of 60, or 21.7%) compared with patients receiving cyclosporine (19 of 50, or 38%) (p=0.025). However, significantly more patients in the tacrolimus group also developed fungal infections. This observation suggested that the relative degree of overall immunosuppression was higher in the tacrolimus group, thereby explaining the lower incidence of acute rejection and BO. A study on the effect of conversion from cyclosporine to tacrolimus in 15 patients with established BO showed a significant reduction in the monthly decline in FEV1 after administration of tacrolimus (1.1 vs 5.3%; p=0.002). buy antibiotics
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Although no protocol is universally accepted for the treatment of BO, augmentation of corticosteroids and cytolytic therapy have been used as initial therapies in the past. Occasionally, presumed acute rejection (ie, an abrupt decline of a previously stable lung function, absence of infection, and nondiagnostic or inadequate histologic examination) may be the initial manifestation of BO; it is treated with augmented steroids. Methylprednisolone, 0.5 to 1 g IV daily for 3 consecutive days, is followed by a 3- to 4-week tapering course of prednisone back to baseline. While a second course of augmented corticosteroids might have been administered years ago, if the FEV1 fails to improve within approximately 4 weeks, antilymphocyte antibody preparations now are often used next. Read the rest of this entry »
Clinical Course of BO
Three distinct patterns of presentation and progression in the clinical course of BO have been described. The first pattern is characterized by a rapid onset followed by a relentlessly progressive course, usually leading to death due to respiratory failure within 1 year of diagnosis. The second pattern is characterized by a similar rapid onset and initial rapid decline, but stabilization of lung function follows. The third pattern is characterized by an insidious onset and chronic deteriorating course. At the time of diagnosis, there are no parameters to predict the different courses. After diagnosis of BO, the mean survival of all affected patients was 66, 44, 37, and 10% after 1, 3, 5, and 10 years, respectively. The main complications of BO are superimposed infections, which are responsible for about 60% of BO-related deaths, and progressive hypoxemia and hypercapnia. Read the rest of this entry »
Ventilation/perfusion scanning in BO usually reveals a decline in ventilation that is most prominent in the peripheral parts of the lung. In patients with BO after single lung transplantation for primary pulmonary hypertension, the decline in ventilation with well preserved perfusion often results in severe ventilation/perfusion mismatch.
Bronchoscopy and Lung Biopsy
In the clinical setting, BAL has not as yet been useful in the detection of BO. Neither total cell counts nor cell differentials in the BAL fluid are diagnostic. Increased lymphocyte cell counts are often obtained in acute rejection in contrast to BO. An increased neutrophil count has been reported in BO. However, increased neutrophils may reflect sampling in larger airways, which could indirectly be a sign of occluded smaller distal airways Reading here generic allegra. The most consistent clinical observation from BAL in patients with BO is the markedly reduced fluid return. While its utility in BO is questionable, BAL—with or without TBB—remains the method of choice to diagnose the pulmonary infections that often complicate BO. Read the rest of this entry »