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Cystic fibrosis (CF) is a complex multisystemic disease requiring specialized care. It is characterized by progressive pulmonary decline, with intermittent worsening of lung function, often called pulmonary exacerbations. Eighty-five percent of all deaths from CF are a result of pulmonary disease, and pulmonary exacerbations are associated with decline in lung function. Treating pulmonary exacerbations requires a multifaceted approach and includes a multidisciplinary team composed of a physician, nurse, respiratory therapist, physical therapist, and nutritionist. Recently, the Cystic Fibrosis Foundation published guidelines addressing the comprehensive treatment of pulmonary exacerbations. This article outlines the treatment goals established by these guidelines, including the evaluation and treatment of comorbid conditions (eg, CF-related diabetes) and serious complications associated with CF exacerbations (eg, pneumothorax). Proper treatment of pulmonary exacerbations in CF patients will continue to improve their health and quality of life.

Background: Sleep impairment has been described in patients with cystic fibrosis (CF). Pain is a known cause of sleep disturbance and as pain is commonly reported in patients with CF, we sought to find an association between impaired sleep quality and pain., Methods: Fifty adult CF patients completed surveys of pain and sleep quality. The results were analyzed with additional clinical data including age, sex, nutritional status, and lung function., Results: Thirty-two patients (64%) reported recent pain and 33 patients (66%) reported abnormal sleep quality. The patients with pain report worse sleep quality than those without pain (p=0.006). There was a strong correlation between impaired sleep quality and pain (p<0.0001)., Conclusions: We found that pain and poor sleep quality are reported in a majority of adult CF patients and there is a strong correlation between the two. This will have important clinical implications in the evaluation and treatment of adult patients.

The clearance of secretions from the lungs of patients with cystic fibrosis (CF) is an important component in the fight to preserve their lung function. There is excessive inflammation in the airways of these patients, which is thought to be exaggerated by ineffective mucociliary clearance and bacterial infection. In 2005 the Cystic Fibrosis Foundation formed the Pulmonary Therapies Committee to review all of the medical literature on the various airway-clearance therapies used in treating CF lung disease. The recommendations were: an airway-clearance therapy should be performed by all patients with CF, no form of airway-clearance therapy stood out as being superior to another, and that patients may express a preference of one therapy over another. They also concluded that aerobic exercise is beneficial to patients with CF, as it is to everyone, and that exercise should be a component to the overall health routine of patients with CF. The challenge for respiratory and physical therapists together with the patient/family is to develop a plan of attack through the use of various airway-clearance therapies. The respiratory and physical therapists are integral in helping patients and families develop airway-clearance routines that aid in the removal of the secretions that cause airway obstruction. There is a wide range of airway-clearance therapies that therapists can choose from when they are teaching the patients and family members the strategies of secretion removal. The questions are: What therapy is best for what age or stage of lung disease? What therapies will the patient do? And which therapies will be covered by medical insurance? These are all fundamental questions that must be answered when guiding families in finding therapies that are effective and appropriate for each CF patient's unique situation.

Earlier diagnosis, treatment of exacerbations, and the use of long-term therapies have all improved the lifespan of patients with cystic fibrosis (CF). However, the natural history of CF airways disease remains one of worsening bronchiectasis and obstructive airways impairment. The progression of airways disease leads to eventual respiratory failure, but some will suffer other acute respiratory complications that require intervention, including pneumothorax, massive hemoptysis, and respiratory failure. Here I discuss the pathophysiology of these complications and the patient-related and treatment-related factors associated with their occurrence. Knowledge of these associations may play great importance in treatment decisions regarding the care of the patient and the respiratory therapist should be aware of the implications. Since disease severity is associated with all 3 conditions, aggressive treatment of the underlying condition is imperative, which includes the performance of airway-clearance therapies. Though some might argue that airway-clearance therapies might aggravate or even precipitate complications such as hemoptysis and pneumothorax, others will defend that there are airway-clearance therapies that might be safely performed. Aerosolized medications such as dornase alfa and tobramycin have been associated with a lower incidence of massive hemoptysis and are recommended therapies for patients with advanced airways disease, yet they are also associated with a higher incidence of pneumothorax, which suggests careful assessment of their potential bronchospastic effect in patients with advanced airways disease. The respiratory therapist also plays a key role in the care of the patient with respiratory failure. Here is also discussed the role of ventilatory support and airway-clearance therapies in the patient with advanced stage disease. Now, more than ever, the patient needs caregivers with the knowledge and sensitivity to provide appropriate palliative care.

Early diagnosis, treatments of acute exacerbations, and chronic therapies have all improved the lifespan of cystic fibrosis patients; however, the natural history remains one of worsening bronchiectasis and obstructive airways impairment. The progression of disease leads to eventual respiratory failure, but some will have other acute respiratory complications that require intervention. In this report, we review the most common life-threatening respiratory complications of cystic fibrosis, including pneumothorax, massive hemoptysis, and respiratory failure.

Since the discovery of the gene associated with cystic fibrosis (CF), there have been considerable advances in our understanding of the mechanisms of disease. Although we are identifying patients with milder manifestations of disease, there are a number of patients who are not diagnosed until adulthood. There is a movement for earlier intervention, so there is increasing interest in making the diagnosis of CF in the asymptomatic patient. With more sophisticated testing, we are able to make the diagnosis in the newborn or even the fetus. In this report, we discuss our current approach to making a diagnosis of CF.

Background: Cystic fibrosis (CF) remains a lethal condition where a palliative approach is often taken at the end of life. We wanted to evaluate how lung transplantation impacts end of life care in adult CF patients., Methods: Data were abstracted using a standardized data collection instrument from all outpatient and inpatient records of adult CF patients with an FEV1< or =30% or prior lung transplantation followed at our Center. Comparisons were made between those who were listed/received lung transplant and those who were not listed., Results: A total of 41 patients met the entry criteria. Of these, 63% (n=26) were referred for lung transplant evaluation and 39% (n=16) had undergone lung transplantation. Of these 41, 59% (n=24) are deceased. The majority of deceased patients expired in an acute care hospital (63%, n=15). There was no difference in site of death between the two groups (hospital versus home). However, listed/transplanted patients were more likely to die in an intensive care unit setting compared to patients not listed/transplanted (p=.013)., Conclusions: Most of our CF patients' deaths occurred in an acute care hospital. Lung transplant significantly alters site of death and shifts it from medical floors to the intensive care unit.

Background: Cystic fibrosis (CF) patients often have widespread inflammatory paranasal sinus disease with an increased incidence of frontal, maxillary, and sphenoid hypoplasia. The most common genetic defect in CF is the delta F508 mutation. The effect of specific CF genotypes on phenotypic sinus development and infections is not well understood. The purpose of this study was to determine whether the homozygous delta F508 mutation is associated with an increased incidence of sinus hypoplasia when compared with other mutations., Methods: This study is a retrospective review of all adult patients seen at our CF center from 1996 to 2005. Patients > or =18 years old with a CF diagnosis using genetic and sweat chloride testing and sinus CT scans were included. Frontal sinus aplasia/hypoplasia and maxillary and sphenoid sinus hypoplasia were documented using published criteria. Data collected included patient demographics, genetic mutations, and prior sinus surgeries., Results: Forty-five patients were identified with an average age of 32 years (range, 18-48 years). Thirty-one patients had prior sinus surgeries. Delta F508 homozygotes (n = 25) had a significantly increased frequency of underdeveloped frontal (98%), maxillary (70%), and sphenoid (100%) sinuses (p < 0.001) when compared with other mutations (69, 8, and 50%, respectively)., Conclusion: CF patients homozygous for the delta F508 mutation have a greater incidence of hypoplastic or underdeveloped sinuses. Whether this is secondary to an increased frequency of sinus infections or a phenotypic expression of the genetic mutation itself remains an area for further investigation.

Patients with cystic fibrosis (CF) often need long-term implanted vascular-access devices for intravenous antibiotics for chronic lower respiratory tract infections. These devices are not without complications, including infection, occlusion, and vascular thrombosis. Such thrombosis can result in superior vena cava (SVC) syndrome due to the position of the catheter proximal to the right atrium. SVC syndrome in CF patients, however, is rarely reported in the literature, suggesting that its incidence is uncommon. We describe three patients with SVC syndrome as a consequence of implanted vascular-access devices.

Background: Spontaneous pneumothorax is a complication that is commonly reported in patients with cystic fibrosis (CF). An understanding of the pathophysiology of this complication and its consequences is important for the management of patients with CF., Objective: To identify risk factors associated with pneumothorax and to determine the prognosis of CF patients following an episode of pneumothorax., Design: A retrospective observational cohort study of the National Cystic Fibrosis Patient Registry between the years 1990 and 1999., Patients: The registry contained data on 28,858 patients with CF who had been followed up over those 10 years at CF centers across the United States., Results: Pneumothorax occurred with an average annual incidence of 0.64% and in 3.4% of patients overall. There was no increased occurrence by sex, but CF was more prevalent in older patients (mean [+/- SD] age, 21.9 +/- 9.1 years) with more severe pulmonary impairment (nearly 75% of patients with FEV1 of < 40% predicted). The principal risks associated with an increased occurrence of pneumothorax included the presence of Pseudomonas aeruginosa (odds ratio [OR], 2.3), Burkholderia cepacia (OR, 1.8), or Aspergillus (OR, 1.3) in sputum cultures, FEV1 < 30% predicted (OR, 1.5), enteral feeding (OR, 1.7), Medicaid insurance (OR, 1.1), pancreatic insufficiency (OR, 1.4), allergic bronchopulmonary aspergillosis (OR, 1.5), and massive hemoptysis (OR, 1.4). There is an increased morbidity (eg, increased number of hospitalizations and number of days spent in the hospital) and an increased 2-year mortality rate following pneumothorax., Conclusion: Pneumothorax is a serious complication in CF patients, occurring more commonly in older patients with more advanced lung disease. Nearly 1 in 167 patients will experience this complication each year. There is an attributable mortality to the complication and considerable morbidity, resulting in increased health-care utilization and a measurable decline in lung function.

Background: Massive hemoptysis is a complication commonly reported in patients with cystic fibrosis (CF). An understanding of the pathophysiology of this complication and its consequences is important for the management of patients with CF., Objectives: To identify risk factors associated with massive hemoptysis, and to determine the prognosis of patients following an episode of massive hemoptysis., Design: A retrospective, observational cohort study of the National CF Patient Registry between the years 1990 to 1999., Patients: The Registry contained data on 28,858 patients with CF observed over 10 years at CF centers across the United States., Results: Massive hemoptysis occurred with an average annual incidence of 0.87% and in 4.1% of patients overall. There was no increased occurrence by sex, but it was more prevalent in older patients (mean age, 24.2 +/- 8.7 years [+/- SD]) with more severe pulmonary impairment (nearly 60% of patients who had an episode of massive hemoptysis had FEV1 < 40% predicted). The principal risks associated with an increased occurrence of massive hemoptysis included the presence of Staphylococcus aureus in sputum cultures (odds ratio [OR], 1.3) and diabetes (OR, 1.1). There was an increased morbidity (eg, increased hospitalizations and hospital days) and an increased 2-year mortality following massive hemoptysis., Conclusion: Massive hemoptysis is a serious complication in CF patients, occurring more commonly in older patients with more advanced lung disease. Nearly 1 in 100 patients will have this complication each year. There is an attributable mortality to the complication and considerable morbidity, resulting in increased health-care utilization and a measurable decline in lung function.

The diagnosis of cystic fibrosis (CF) generally is made within the first few years of life, although some cases will not be diagnosed until adulthood. For most patients the diagnosis is suggested by typical CF-related symptoms such as chronic respiratory infection or maldigestion. The authors describe an adult patient with newly diagnosed CF whose presenting abnormalities consisted of hypokalemia and metabolic alkalosis. These are known complications of CF but are not common presenting features that lead to the diagnosis of CF. The authors discuss their patient's presentation and review his metabolic manifestations of CF.

Introduction: Patients with cystic fibrosis (CF) suffer from chronic infection of the airways, and typical CF therapies include aerosolized medications. There is recent evidence that home nebulizers become contaminated by bacteria, causing concern that nebulizers may be a source of bacterial infection of the lower airways. A recent consensus document on infection-control issues for the CF population included recommendations on cleaning and disinfecting nebulizers., Methods: We surveyed 39 patients and their parents, as well as 54 respiratory therapists, regarding their routine nebulizer use and maintenance practices., Results: All the patients used at least one nebulized medication, and they used a variety of nebulizers, obtained from a wide variety of sources. Thirty percent of the patients used nebulizers well beyond the manufacturer's recommended replacement date. Ninety percent of the patients rinsed their nebulizers following use, but only 15% performed any routine disinfection. The respiratory therapists' nebulizer cleaning methods were widely disparate, with only 70% performing some method of rinsing. The respiratory therapists' self-report of cleaning methods and their instructions to patients regarding frequency of cleaning were so diverse that no standard is evident., Conclusion: This study demonstrates that CF patients and their respiratory therapists should immediately address and improve their nebulizer cleaning methods and replacement practices. There should be more focus on teaching patients to regularly clean and replace nebulizers.

The pharmacokinetics of many drugs are altered in patients with cystic fibrosis (CF), often necessitating different dosage requirements than those used in non-CF patients. The objective of this study was to determine the pharmacokinetics of linezolid, an antibiotic with good activity against gram-positive organisms such as methicillin-resistant Staphylococcus aureus, in patients with CF so that dosage requirements could be established. Twelve adult patients (6 male) ranging in age from 22 to 39 years were studied. A single 600-mg dose was administered intravenously over 0.5 h, and plasma samples were collected at 0 (predose), 0.5, 0.75, 1, 2, 4, 8, and 24 h. Linezolid concentrations were determined with a validated high-performance liquid chromatography assay. Pharmacokinetic parameters were estimated using standard noncompartmental methods. Blood chemistry and hematologic indices were determined before and after the study for safety purposes. All patients completed the study without encountering any adverse reactions. The pharmacokinetic parameters, while variable, with half-lives varying from 1.76 to 8.36 h, were similar to those previously described in other populations. Mean (+/- standard deviation) values for pharmacokinetic parameters of interest were as follows: elimination rate constant, 0.21 (0.11) h(-1); half-life, 4.41 (2.43); volume of distribution at steady state, 0.87 (0.19) liters/kg of body weight; and total body clearance, 0.12 (0.06) liters/h/kg. No patient would have achieved the pharmacodynamic target of an area under the concentration-time curve/MIC ratio of 83 h for pathogens for which the MIC was 4 micro g/ml. Patients with inadequate clinical responses to linezolid may require more frequent dosing.

We previously surveyed cystic fibrosis (CF) center directors and adult patients with CF to assess their perceptions regarding transition from a pediatric to an adult setting. An important finding in those studies was a lack of standard programs for transfer of young adults with CF from pediatric to adult care settings. Patients with CF typically receive care from clinics utilizing a multidisciplinary approach, suggesting that every member of the CF team can impact the transition process. Our purpose in this study was to gain an appreciation for various team members' perspectives on transition. An Internet survey was offered to all CF centers across the country to be completed by team members, excluding physicians. We received 291 completed surveys, nearly half completed by nurses, but our respondents included social workers, nutritionists, respiratory therapists, and a few team members with other training. Nearly half of the respondents work for both pediatric and adult teams. The majority of respondents (71.8%) reported that their adult patients receive care from an internist in a separate adult program, but nearly 20% reported that a pediatrician follows their adult patients. A minority thought that age (37.4% of respondents), marriage (16.2%), and pregnancy (27.1%) were criteria for transfer, though most (86.2%) suggested that patients should be transferred by age 21 years. Criteria precluding transfer included patient/family resistance (45%), disease severity (34%), and developmental delay (31.3%). It was uncommon (11.4%) for an introduction to the concept of transition at the time of diagnosis. Over one-half of patients did not meet the adult team until time of transfer. Team members' perceptions of patients' concerns were similar to what we had previously measured in physicians, again far greater than what we have measured in patients themselves. In many ways, what we have measured here in team members reflects what we have reported by physicians, demonstrating slow development of standard transition programs and an overestimate of patients' concerns regarding transition. These differences may impede the successful transition of patients into an adult program. It is clear from this study that team members have an interest in and opinions on transition, and are likely play a vital role in the transition process. Standard programs of transition should be developed, and team members should be engaged in that process., (Copyright 2004 Wiley-Liss, Inc.)

The airways of the patient with cystic fibrosis (CF) are chronically infected. There is excess mucus within the airways and, because of the chronic infection, the mucus also contains bacteria and inflammatory cells. Mucociliary clearance is impaired in patients with CF, and patients become dependent upon cough and other techniques to clear their airways of the thick sputum. This review discusses the various techniques and medications that have been demonstrated to be effective at assisting the clearance of the excess secretions in the CF airways. No single method has been proven to be better than the others, and not all patients will benefit, or use, the same techniques. Therefore, the methods of airway clearance must be tailored for each patient to assure effective therapy.

Spontaneous pneumothorax is a common complication in patients with cystic fibrosis (CF). It is thought to occur more frequently in patients with more advanced disease. Recommendations on the management of pneumothorax in CF are based on retrospective analyses and reports from CF centers. The following is a review of what has been published regarding the incidence and management of pneumothorax in this population, with some comment on the pathogenesis of the complication.

There is a growing population of adults with cystic fibrosis (CF) and a need for development of adult CF programs. Recommendations for transfer of patients from pediatric care to an adult program include a transition program. The purpose of this study was to survey adult CF patients to assess their own concerns regarding this issue. A survey was sent to all 1,288 members of the International Association of Cystic Fibrosis Adults (IACFA), with a response rate of 25.9% (n = 334). The majority of patients (81.2%) received care from a CF center; the major difference between those seen at a CF center and those seen at another facility was proximity to a CF center. Nearly one-fourth of patients seen at a CF center continued to receive care from a pediatrician even though a CF-trained internist was available; though these patients were younger, their mean age was still about 30 years. Patients seen by a pediatrician were more like to be students and to live with their parents. Those patients seen in an adult program described a variety of criteria for their transfer to the adult pro-gram, but there were no consistent findings to suggest a standard transition program. Indeed, many patients did not meet the adult team until the time of the transfer. Most importantly, the patients reported their level of concern about transfer as minimal, far less than what CF physicians had perceived. These differences may impede the successful transition of patients into an adult program.

Munchausen syndrome is a pattern of abnormal behavior in which patients repeatedly present with symptoms that have no organic basis and are intentionally simulated or produced in order to assume the sick role and gain admission to the hospital. A 25-year-old white woman presented to our adult cystic fibrosis (CF) program and gave a detailed history consistent with a diagnosis of CF, a complicated disease with multiorgan involvement that is difficult to feign. However, discrepancies in her history were noted and objective measures of disease were inconsistent, including evidence of a fabricated sweat chloride result. We describe the classic characteristics of Munchausen syndrome that our patient exhibited, and report this unusual presentation of Munchausen syndrome to be consistent with the recommendation of reporting such cases to other physicians. Such knowledge is likely to result in less harm to the patient through unnecessary testing and treatment.

Background: Pulmonary complications are common in patients who have undergone esophagectomy. There are no good predictive variables for these complications. In addition, the role that preoperative treatment with chemotherapy and radiation may play in postoperative complications remains unclear., Methods: We performed a retrospective review of all patients who underwent esophagectomy by a single surgeon at our institution over a 6-year period. Data were analyzed for a correlation between patient risk factors and pulmonary complications, including mortality, prolonged mechanical ventilation, and hospital length of stay., Results: Complete data were available on 61 patients. Nearly all patients had some pulmonary abnormality (eg, pleural effusion), although most of these were clinically insignificant. Pneumonia was the most common clinically important complication, and 19.7% of patients required prolonged ventilatory support. Significant risk factors identified included impaired pulmonary function, especially for patients with forced expiratory volume in 1 second (FEV1) less than 65% of predicted, preoperative chemoradiotherapy, and age., Conclusions: Impaired lung function is a significant risk factor for pulmonary complications after esophagectomy. Patients with FEV1 less than 65% of predicted appear to be at greatest risk. There also seems to be an associated risk of preoperative chemoradiotherapy for pulmonary complications after esophagectomy.

Hepatopulmonary syndrome (HPS) is an infrequent complication of liver cirrhosis. Orthotopic liver transplantation (OLT) has gained increasing acceptance as a treatment modality for HPS, although there have been reports of HPS developing after OLT with documented recurrence of cirrhosis. We describe the case of a 9-year-old boy who underwent OLT at 7 months of age because of biliary atresia. He subsequently developed HPS in the setting of chronic rejection without cirrhosis or evidence of portal hypertension. Re-OLT resulted in resolution of HPS and a good clinical outcome.

There is a growing population of adults with cystic fibrosis (CF) and a need for development of adult CF programs. Recommendations for transfer of patients to an adult program include a transition program. Our goal was to assess the current status of transition programs in US CF centers. In addition, we sought to determine the problems related to the transfer of patients to adult programs as perceived by CF center program directors. A survey was sent in 1998 to 110 pediatric and 44 adult program directors at CF centers approved by the Cystic Fibrosis Foundation (CFF), with a response rate of 65.5% and 72.7%, respectively: 22.2% of pediatric centers reported having a non-CFF-approved adult program, and 38.9% had no specific adult program. About one fifth of pediatric centers cited lack of an adult CF physician as an impediment to establishing an adult program. Age (82% of programs; mean, 18.5 years), but not marriage (17.1%) or pregnancy (24.8%), was used as a criterion for transfer. Criteria precluding transfer included patient/family resistance (51.4%), disease severity (50.5%), and developmental delay (46.7%). The concept of transfer is introduced to the patient and family at the time of diagnosis in a minority (14%) of programs. Over one half of the patients did not meet the adult team until the time of transfer. Pediatricians reported higher perceived parent, patient, pediatric staff, and adult staff concerns about transition issues than did adult program directors. We conclude that there is a lack of standardized programs for transfer of CF patients from a pediatric to an adult care setting, and that there are differences between pediatric and adult program directors' perceptions of concerns that CF patients, their families, and the medical teams have about transfer. These differences may impede the successful transition of patients into an adult program.

Study Objectives: The purpose of this study is to assess the psychological profiles of adult patients with cystic fibrosis (CF) and to investigate predictors of patients' psychological status., Patients and Methods: Thirty-four adults with CF completed a battery of psychological testing including the Minnesota Multiphasic Personality Inventory-2, Beck Depression Inventory, and State-Trait Anxiety inventory. These were compared to health status data, including pulmonary function testing and nutritional status measures., Results: As a group, adults with CF did not demonstrate significant levels of depression, anxiety, or other psychopathology. Results were not affected by age, sex, or severity of disease. Male gender predicted higher scores for depression and anxiety, and better lung functioning predicted less anxiety. Having a higher level of psychosocial support emerged as a strong predictor of better psychological functioning., Conclusions: Overall, adults with CF report relatively healthy psychological functioning. Better lung function and a strong social support system predicted better psychological functioning, which may have implications for clinical intervention.

Study Objective: To compare the efficacy of constant-infusion ceftazidime (CTZ) with that of traditional intermittent dosing in a pilot trial., Design: Prospective, crossover trial., Subjects: Five adults with cystic fibrosis requiring intravenous antibiotic therapy for pulmonary exacerbations of the disease., Interventions: Patients were initially treated with standard CTZ 2 g 3 times/day for 10 days. At the next hospitalization patients were crossed over and CTZ was administered as a constant infusion at a rate determined to achieve a serum concentration 6.6 times the minimum inhibitory concentration (MIC) of the least susceptible Pseudomonas aeruginosa isolate., Measurements and Main Results: The pharmacokinetics of CTZ were determined, as were MICs for all P. aeruginosa isolates. Outcome parameters of interest were changes with therapy in white blood cell count, P aeruginosa density in sputum, and pulmonary function test results. Differences in these parameters for the two forms of administration were not significant. With the exception of one patient who received 6 g/day with both regimens, the average reduction in dosage with the constant infusion was 50%., Conclusion: These preliminary data suggest that constant-infusion CTZ may be as safe and efficacious as intermittent dosing.

Bactericidal activity, historically assessed by in vitro tests which employ fixed drug concentrations, may also be evaluated in in vitro pharmacodynamic models in which in vivo pharmacokinetics and bacterial growth conditions can be simulated. However, systematic comparisons between the two methods are lacking. We evaluated the bactericidal activities of ceftazidime, at two different concentration/MIC ratios (C/MICs), against 10 clinical isolates of Pseudomonas aeruginosa in a two-compartment model with continuous-infusion conditions and a 2-h half-life. These values were compared to those determined by traditional 24-h time-kill (TTK) methods at the same C/MICs. Bactericidal activities were compared by using area under the colony count-time curves. Antibiotic exposure (area under the drug concentration-time curve) was also evaluated. Although bactericidal activity appeared greater by the TTK method (P = 0.05), when it was normalized for drug exposure, these differences disappeared (P = 0.2). This disparity was likely due to differences in drug exposure in the TTK method and in the peripheral compartment of the model (site of bacteria) over the first 8 h of the experiment, during which the antibiotic accumulated to target concentrations. This suggests that the bactericidal effects with constant antibiotic concentrations are similar in the two methods; however, this may not hold true with fluctuating drug concentrations. Further, results from the pharmacodynamic model may theoretically be more relevant, as in vivo pharmacokinetics and bacterial growth conditions call be more faithfully simulated.

The concentration/MIC (C/MIC) ratio maximizing the bactericidal activity of ceftazidime against 10 Pseudomonas aeruginosa isolates from cystic fibrosis patients was identified. Bactericidal activity was assessed by determining the percent difference in the area under the killing curve at each C/MIC ratio for all of the isolates from that of their growth control. The percent effect at each C/MIC ratio was fitted to a sigmoidal Emax model with maximum bactericidal activity defined as the C/MIC ratio that produced an effect that was 90% of the Emax. Our results suggest that at least some isolates may require higher C/MIC ratios than previously reported for maximal activity.

Fowler (Fowler, W.S., 1954, J. Appl. Physiol. 6:539-545) showed that rebreathing, despite worsening PCO2 and O2 saturation, relieved the distress of breathholding; he suggested a role for vagal input in the relief. We studied effects on respiratory sensation of breathholding and rebreathing in normals, patients with bilateral lung transplants (LT), who have a decrease in number of pulmonary stretch receptors (PSR), and heart transplant recipients (HT). Subjects held their breath until distress became intolerable, rebreathed various combinations of CO2 and O2, then performed another maximal breathhold. Respiratory distress was rated continuously (visual analog scale) by each subject. Both LT and HT had earlier onset of and more rapidly developing distress during breathholding, resulting in shorter breathhold times, than normals. Relief with rebreathing was neither as rapid nor as great in LT as in HT and normals. Our findings suggest that mechanisms that produce respiratory distress in HT and LT are similar, but differ from normals. However, reduction in distress on rebreathing is more rapid and greater in HT and normals than in LT. This is compatible with the loss during rebreathing of the inhibitory effect of PSR input on neural mechanisms that lead to respiratory distress.

It is well known that rebreathing relieves the respiratory distress of maximal breathholding despite worsening blood gases, and it has been suggested that vagal input has a role in ameliorating this sensation via activation of pulmonary stretch receptors (PSR). However, it is believed by divers that expiration can lead to partial relief of distress of breathholding at total lung capacity (TLC) allowing a prolongation of breathholding. We studied the independent effects of an expiration and an inspiration on relief of respiratory distress of breathholding. Subjects held their breath at TLC until distress became intolerable, then exhaled to FRC and performed a second breathhold. When distress again became intolerable, subjects inspired to TLC a gas that resembled their exhaled gas and performed a third breathhold. Subjects noted partial relief with both an expiration and an inspiration. However, relief of distress was greater and the subsequent breathhold longer after an inspiration than after an expiration. We suggest that relief of distress after an inspiration is compatible with the inhibitory effect of PSR input; the mechanism of relief that occurs after an expiration is as yet uncertain.

It has been suggested that the presence of airway pathogens prior to lung transplantation (LT) in patients with cystic fibrosis (CF) may place these patients at a higher risk for infectious complications after LT. There is particular concern regarding patients colonized with multiresistant Pseudomonas, including P. cepacia, and fungi, including Aspergillus. We report our experience with LT for patients with CF and compare the results with those of patients with LT for other indications. Between January 1990 and March 1993, we performed LT for 27 patients with CF and 32 without CF. Nearly all (89%) of the patients with CF were colonized with P. aeruginosa; many were cultured with P. cepacia (19%) and Aspergillus (63%). The non-CF group rarely had organisms identified pre-LT. No patients with CF underwent pre-LT sinus drainage or received pre-LT treatment for Aspergillus. All of the patients received perioperative antibiotics and a standard regimen of immunosuppression and prophylactic antibiotics. The incidence of infectious complications was the same in the two groups; however, there was an association between obliterative bronchiolitis and pulmonary infections. One of the patients with CF with P. cepacia died as a result of this organism. None of the patients with CF required treatment for Aspergillus post-transplant. We conclude that patients with CF, despite the presence of airway pathogens, are at no greater risk of infectious complications after LT than are other patients.

As lung transplantation has become more successful, the selection criteria have broadened; however, some relative contraindications to lung transplantation are controversial. Some programs consider mechanical ventilation to be a major contraindication to lung transplantation because airway colonization with bacteria may lead to nosocomial infection and respiratory muscle deconditioning may necessitate prolonged postoperative ventilatory support. We report our experience of seven double lung transplant procedures on six patients requiring mechanical ventilation. Five patients with cystic fibrosis required preoperative mechanical ventilation for 7 to 19 days (mean, 10.7 days). One patient with acute lung injury required 115 days of preoperative mechanical ventilatory support. Only the latter patient required prolonged (27 days) postoperative mechanical ventilation because of respiratory muscle weakness; the others were extubated in 1 to 19 days (mean, 7.8 days). No early complications related to bacterial infection were seen. Two patients required temporary hemodialysis for transient kidney failure. Three patients had postoperative neurologic residua; one patient had a transient hemiparesis, and seizures developed in two patients. One patient died 3 months after transplantation from severe central nervous system complications with no evidence of pulmonary problems; and two patients died 17 months after transplantation, one of them receiving a second double lung transplant for obliterative bronchiolitis. Except for the patient who required prolonged preoperative ventilatory support, mechanical ventilation did not appear to play a role in the outcome of these patients. The posttransplantation hospital stay and hospital charges for patients requiring pretransplantation ventilatory support were not significantly different from those for other lung transplant recipients.(ABSTRACT TRUNCATED AT 250 WORDS)

The respiratory distress of breathholding has been shown to be relieved by breathing, even without correction of worsening blood gases (Fowler, 1954). We repeated the study by having untrained normal subjects perform maximal breathholds which were followed by the rebreathing of a gas mixture containing 7.5% CO2 and 8.2% O2, and then by second breathholds. In addition, we had the subjects continuously rate their respiratory distress using a visual analog scale (VAS). The ratings were easy to perform and were highly reproducible on repeated trials in a given subject. Subjects experienced increasing distress during the breathhold, rapid and substantial relief upon rebreathing, and then were capable of performing second breathholds, all consistent with Fowler's results. The findings are consistent with animal studies in which a neural mechanism associated with stimulation of pulmonary stretch receptors inhibits the firing of midbrain neurons which may be involved in transmission to the cortex of sensory information about breathing.