Steven Kesten

Adverse effects of inhaled corticosteroids.

Inhaled corticosteroids are considered by many to be the anti-inflammatory therapy of choice in adult asthma, given their remarkable efficacy and apparent safety. They are presently being prescribed to more patients, at larger doses, and for longer periods of time than ever before. Oropharyngeal candidiasis and dysphonia are the most commonly recognized adverse effects of therapy, but these topical phenomena cause no significant morbidity and are easily managed. By contrast, there is now increasing concern about the potential systemic effects of inhaled corticosteroids. These putative effects may include adrenal suppression, bone loss, skin thinning, increased cataract formation, decreased linear growth in children, metabolic changes, and behavioral abnormalities. Changes in adrenal function have been noted in patients using medications such as beclomethasone dipropionate and budesonide in doses exceeding 1,500 micrograms/day. The clinical relevance of these changes has yet to be clarified. Several short-term and cross-sectional studies have also revealed changes in biochemical markers of bone turnover and retrospective studies have found reduced bone density in asthmatics treated regularly with inhaled steroids. Long-term prospective studies assessing bone density changes remain to be done. Although much controversy exists, there is no unequivocal evidence that conventional doses of inhaled steroids significantly retard bone growth in children. Reports on skin changes, increased cataract formation, and behavioral changes are difficult to interpret because of several confounding factors. Although inhaled steroids should, at the present time, continue to be a recommended therapeutic option to all patients with symptomatic asthma, they should always be used in the lowest dosage compatible with disease control.

Pleural complications in lung transplant recipients

Pleural complications occurred in 30 (22%) of 138 patients after 53 single and 91 double lung transplants between September 1986 and February 1993. These were defined for the purpose of this study as pneumothorax persisting beyond the first 14 postoperative days, recurrent pneumothorax, or any other pleural process that necessitated diagnostic or therapeutic intervention. Overall, a higher pleural complication rate was seen in double lung transplantation (25 of 30) than in single lung transplantation (5 of 30) with no differences noted in the frequency among preoperative diagnostic groups (p > 0.05). Pneumothorax was the most frequent complication, affecting 14 of 30 patients, with 6 of 14 cases occurring after transbronchial biopsy. All pneumothoraces in single (n = 4) and double lung transplantation (n = 10) resolved spontaneously or with chest tube thoracostomy. One patient required placement of a Clagett window after open lung biopsy and another required thoracotomy and pleural abrasion after transbronchial biopsy. Parapneumonic effusion was observed in 4 of 30 double lung transplantations with spontaneous resolution in all cases. Empyema affected 7 of 30 patients and occurred exclusively in the double lung transplant group. Sepsis developed in three of the patients with this complication and they subsequently died. The risk of empyema was independent of preoperative diagnosis (p > 0.05). Of interest, all patients with cystic fibrosis (n = 3) with complicating empyema had Pseudomonas cepacia in the pleural fluid. Other miscellaneous complications included subpleural hematoma, chylothorax, and hemothorax. The latter two necessitated thoracic duct and bronchial artery ligation, respectively. In summary, a significant proportion of lung transplant recipients will have pleural space complications. The vast majority of these will resolve spontaneously or with conservative procedures. These complications were not related to preoperative diagnosis nor associated with a significant prolongation of hospital stay (p > 0.05). Empyema is the only pleural space complication associated with increased patient mortality and, as such, is an important clinical marker for those at risk for sepsis and death.

Diaphragmatic paralysis: A complication of lung transplantation

BACKGROUNDnDamage to the phrenic nerve, either unilaterally or bilaterally, is a well-documented complication of cardiac operation, but less commonly reported after lung transplantation.nnnMETHODSnA retrospective review of 185 single and sequential single lung transplant procedures was performed at The Toronto Hospital. Objective confirmation (fluoroscopy or ultrasound) of diaphragmatic paralysis was found in 6 patients. Paralysis was unilateral in 5 patients (all were left sided) and bilateral in 1 patient.nnnRESULTSnThe average length of ventilation was 8.2 +/- 9.2 days with an average intensive care unit stay of 11.2 +/- 10.6 days. Mean duration in the hospital was 37.5 +/- 11.1 days. The average length of intensive care unit stay and hospitalization were compared with all other sequential single transplantations performed from approximately the time of the first documented case of diaphragmatic paralysis. Intensive care unit stay and hospitalization for the other (no diaphragmatic paralysis) transplant recipients were significantly shorter (5.3 +/- 2.7 and 29.1 +/- 12.9 days, respectively; p < 0.05). One patient required noninvasive ventilatory assistance via bilevel positive airway pressure in the hospital. One other patient used bilevel positive airway pressure in the hospital and overnight for 6 months after discharge. All patients obtained acceptable lung function and were ambulatory upon discharge from the hospital.nnnCONCLUSIONSnClinically detectable diaphragmatic paralysis is an infrequent complication of lung transplantation and is associated with longer intensive care unit stay and hospitalization, but is not associated with significant adverse outcomes.

INFECTIONS IN LUNG TRANSPLANT RECIPIENTS

Advances in surgical technique and better knowledge of the physiologic and immunologic changes in the transplant population, combined with improved diagnostic tools and treatment strategies, have decreased the likelihood of early and, possibly, late mortality caused by a primary infection. Nevertheless, infection continues to be an important cause of death in both the early and late post-transplant periods. Risk of death attributable to infection after prolonged survival, however, is greatest in the setting of chronic rejection. The most significant advances in antimicrobial management have been in the area of prophylaxis. The effectiveness of prophylaxis against P carinii has virtually eliminated that organism as a cause of significant morbidity. Ganciclovir prophylaxis protocols require refinement but have been proved effective against CMV, although that virus continues to be a major pathogen in lung transplant recipients. Ultimately, a careful monitoring protocol and a high index of suspicion for infection requiring investigation and treatment are necessary in the ongoing care of lung transplant recipients. The approach to infections should be guided by the knowledge of the various factors that increase susceptibility to microorganisms and any previous culture and sensitivity results. As transplant physicians try to increase the donor pool through the use of donors who previously might have been rejected and through the potential of xeno-transplantation, vigilance and research must be maintained.

Aprotinin reduces blood loss in lung transplant recipients

After early experience with perioperative bleeding in sequential single-lung transplant recipients, aprotinin was introduced in an attempt to reduce this complication and the attendant morbidity. Records of sequential single-lung transplantations (n = 33) performed between January 1989 and November 1991 were reviewed to assess the impact of aprotinin on perioperative blood loss and blood product requirements. Recipients were divided according to whether or not they required cardiopulmonary bypass. In patients requiring cardiopulmonary bypass (n = 15), mean estimated postoperative blood loss was 3,000 +/- 500 mL in those who did not receive aprotinin (n = 4) compared with 1,177 +/- 253 mL in those who received aprotinin (n = 11) (p < 0.05). An average of 8.0 +/- 0.7 units of packed red blood cells were administered to patients not receiving aprotinin compared with 3.1 +/- 0.7 units to those who received aprotinin (p < 0.05). Requirements for fresh frozen plasma were similar in each group. There were no differences in blood loss or blood product replacement in the group not undergoing cardiopulmonary bypass (n = 18). Therefore, we conclude that aprotinin decreases postoperative blood loss and blood product requirements in patients undergoing sequential single-lung transplantation under cardiopulmonary bypass.

The Effect of Structured Versus Conventional Inhaler Education in Medical Housestaff

Despite the importance of adequate inhaler technique in the care of asthma and chronic obstructive pulmonary disease, physicians have often been shown to have poor knowledge of correct inhaler use. At present, postgraduate teaching programs appear to leave physicians to acquire inhaler handling skills informally in the context of day-to-day patient care. We undertook the present study to determine if one brief structured educational intervention would be adequate to teach postgraduate physicians inhaler skills that would be retained over long periods of time. We also compared the efficacy of this intervention to traditional education methods. We recruited 52 postgraduate trainees in internal medicine at a large university hospital; 26 were in the educational intervention group and 26 were in the control group. Physicians in the intervention group were asked to respond to a questionnaire on inhaler use and to demonstrate the correct use of a metered-dose inhaler (MDI), an MDI with a pacing chamber and a multidose dry-powder inhaler. These intervention subjects were then instructed on proper inhaler usage by a qualified nurse educator. Eight months later, testing was repeated in the intervention group and was undertaken in the control group. Questionnaire scores were significantly higher in the intervention group at the 8-month follow-up than at baseline (59% vs. 42%; p < 0.05). Similarly, the scores of the intervention group at follow-up were significantly higher than those of the control group (59% vs. 39%; p < 0.05). There was no significant difference between the baseline scores of the intervention group and those of the control group. The mean demonstration score was significantly higher in the intervention group at follow-up than at baseline (68% vs. 39%; p < 0.001) and was also higher than that of the control group (68% vs. 44%; p < 0.001). There was no significant difference between the scores for all devices between the intervention group before education and the control group. Our data show that one brief teaching session is sufficient to produce a sustained improvement in knowledge and handling of inhalers by postgraduate physicians. The knowledge and skills of the physicians educated in our study were not only better than before they had received instruction, but were better than the knowledge and skills of postgraduate trainees from the same institution who had received no formal training. This latter observation suggests a failure of traditional unstructured postgraduate training programs to teach this practical patient care skill.

Assessment of an ambulatory care asthma program.

In response to rising asthma morbidity and mortality, numerous comprehensive asthma programs have been developed. However, few studies have examined critically the effectiveness of such programs or the means by which treatment or outcome is altered. To assess the role of a specialized ambulatory asthma care program, we reviewed the interventions recommended to 344 patients referred for the assessment of asthma. A subset of 127 made return visits 6-12 months following their initial assessment, thereby allowing assessment of behavioral and physiological outcomes. At the initial consultation, the recommended medication changes were: inhaled beta-agonists +6% (p < 0.01), inhaled steroids +58% (p < 0.001), intranasal steroids +8% (p < 0.001), dry powdered formulations +13% (p < 0.01), theophylline -7% (p < 0.001). The percentage of patients using spacer devices increased 8% (p < 0.001). Comparing preassessment values to those at a visit at 6-12 months following assessment, a further 25% of patients taking inhaled steroids at the initial assessment had a change to either the dose, device, or frequency of administration. Mean FEV1 improved from 2.41 +/- 0.08 liters at the initial assessment to 2.64 +/- 0.09 liters at the 6-12-month visit (p < 0.001). There was an increase in the number of patients considered mild and not obstructed, with a corresponding decrease in the number considered moderately and severely obstructed (p < 0.05). The number of emergency room visits was reduced by more than 60% (p < 0.001) in patients followed for at least 6 months. We conclude that an ambulatory asthma program marked by increased use of inhaled anti-inflammatory medications and decreased use of theophylline can produce significant decreases in asthma exacerbations requiring hospital care, emergency room care, or systemic steroids while reducing the prevalence and severity of airflow limitation.