Antibody-Mediated Rejection in a Multiple Lung Transplant Patient: A Case Report

Lung transplant is an effective way to treat many end-stage lung diseases. However, one of the main barriers of allograft organ transplant is still the immunologic rejection of transplanted tissue, which is a response of the HLA molecules. Rejection is a complex process involving both T-cell–mediated delayed-type hypersensitivity reactions and antibody-mediated hypersensitivity reactions to histocompatibility molecules on foreign grafts. We report the case of a 25-year-old female patient with cystic fibrosis who underwent 2 lung transplants because of her initial diagnosis and appearance of bronchiolitis obliterans syndrome after the first transplant. Only 13 months after the second transplant, despite the therapies applied, a new rejection occurred associated with high mean fluorescent intensity donor-specific antibody levels, which resulted later in the death of the patient. The present case draws attention to the importance of matching HLA molecules between donor and recipient in addition to immunosuppressive therapy.     

“White‐Out” After Lung Transplantation: A Multicenter Cohort Description of Late Acute Graft Failure

Graft failure represents a leading cause of mortality after organ transplantation. Acute late‐onset graft failure has not been widely reported. The authors describe the demographics, CT imaging–pathology findings, and treatment of patients presenting with the latter. A retrospective review was performed of lung transplant recipients at two large‐volume centers. Acute late‐onset graft failure was defined as sudden onset of bilateral infiltrates with an oxygenation index <200 without identifiable cause or concurrent extrapulmonary organ failure. Laboratory, bronchoalveolar lavage (BAL), radiology, and histology results were assessed. Between 2005 and 2016, 21 patients were identified. Median survival was 19 (IQR 13–36) days post onset. Twelve patients (57%) required intensive care support at onset, 12 (57%) required mechanical ventilation, and 6 (29%) were placed on extracorporeal life support. Blood and BAL analysis revealed elevated neutrophilia, with CT demonstrating diffuse ground‐glass opacities. Transbronchial biopsy samples revealed acute fibrinoid organizing pneumonia (AFOP), organizing pneumonia, and diffuse alveolar damage (DAD). Assessment of explanted lungs confirmed AFOP and DAD but also identified obliterative bronchiolitis. Patients surviving to discharge without redo transplantation (n = 2) subsequently developed restrictive allograft syndrome. This study describes acute late‐onset graft failure in lung allograft recipients, without known cause, which is associated with a dismal prognosis.     

Chronic lung allograft dysfunction after lung transplantation: the moving target

Chronic lung allograft dysfunction is a major challenge in long-term management of lung transplant recipients. Both alloimmune-dependent factors (rejection) and alloimmune-independent factors contribute to the development of chronic lung allograft dysfunction. Thus, use of the term “chronic rejection” tends to be intentionally avoided among specialists in the field, although “chronic rejection” is still an acceptable lay word understood by many patients. Several different phenotypes have been identified in chronic lung allograft dysfunction, including restrictive allograft syndrome, neutrophilic reversible allograft dysfunction, and fibrous bronchiolitis obliterans syndrome. Restrictive allograft syndrome is characterized by restrictive physiology and peripheral foci of inflammation and fibrosis, which contrasts the obstructive physiology and pathological foci in small airways in conventional bronchiolitis obliterans syndrome. Among patients with bronchiolitis obliterans syndrome, there is a subpopulation that responds relatively well to azithromycin. Because these patients show airway neutrophilia, this subtype of chronic lung allograft dysfunction was named neutrophilic reversible allograft dysfunction. Conversely, patients with bronchiolitis obliterans syndrome unresponsive to azithromycin show airway fibrosis with less inflammation (fibrous bronchiolitis obliterans syndrome). In general, restrictive allograft syndrome shows poorer survival than does bronchiolitis obliterans syndrome, and early-onset bronchiolitis obliterans syndrome (within 2 years) shows a worse prognosis than does late-onset bronchiolitis obliterans syndrome. Until preventive and therapeutic options are refined, chronic lung allograft dysfunction will remain a major life-limiting factor. It has significant psychological, physical, social, and economic impacts. Early introduction of palliative care is another important strategy to improve patients’ quality of life.     

Delirium Development After Lung Transplantation: An Intraoperative Assessment

BackgroundThis study aimed to evaluate the relationship between intraoperative hemodynamic and laboratory parameters with postoperative delirium development after lung transplantation.MethodsA total of 77 patients who underwent lung transplantation in a single center were included in the study. Demographic and clinical data recorded at critical intraoperative stages (after induction [T1], after bilateral lungs are dissected [T2], while the patient is ventilated for 1 lung [T3], while the unilateral transplanted lung is ventilated [T4], while bilateral transplanted lungs are ventilated [T5], and after the thorax is closed [T6]), postoperative complications, mechanical ventilation duration, intensive care, and hospitalization durations and mortality rates were recorded.ResultsA total of 83.1% of the 77 patients were male, and the mean (SD) age was 47.56 (12.95) years. The mean body mass index (calculated as weight in kilograms divided by height in meters squared) was 23.30 (3.99), and the median Charles Comorbidity Index (CCI) was 1. The diagnosis of 36.4% of the patients was chronic obstructive pulmonary disease. Delirium was seen in 51.9% of the patients. Age, CCI, intraoperative mean arterial pressure changes, lactate levels, mechanical ventilation duration, and hospital stay were all associated with delirium development.ConclusionAge, CCI, duration of mechanical ventilation, and hospital stay were independent predictors of postoperative delirium development. We believe that our study will be a guide for future prospective randomized controlled studies.     

Asynchronous independent lung ventilation

The use of asynchronous independent lung ventilation is described in a patient presenting with acute respiratory failure due to a severe unilateral pneumonia. A polyvinyl chloride (Portex) double-lumen tube was inserted through a tracheostomy and the lungs ventilated independently using a combination of a Cape ventilator and a Servo 900B ventilator.     

Results of Lung Transplantation in Patients With Cystic Fibrosis

Lung transplantation (LT) is the only available option for patients with cystic fibrosis (CF) with end-stage lung disease. We reviewed our experience with LT in patients with end-stage CF (CFLT) to identify variables associated with survival and to compare the results with other indications for LT (OILT). Between October 1993 and October 2007, we performed 259 consecutive LTs in 250 patients for treatment of various end-stage pulmonary conditions. The indications for LT were CF in 78 patients idiopathic pulmonary fibrosis in 76, COPD in 64, bronchiectasis in 11, alfa-1-antitrypsin deficit in 5, primary pulmonary hypertension in 4, bronchiolitis obliterans syndrome in 4, and other indications in 11. Our study group comprised 78 patients with CF (30.11%) (CFLT). We observed significant differences in the actuarial survival between the CFLT and OILT groups. Perioperative mortality and the incidence of bronchiolitis obliterans syndrome were comparable in both groups. We found that in patients with CF, LT performed under urgency code (mechanical ventilation) showed no significant difference from LT performed electively insofar as long-term survival, early death, or perioperative death. The functional results in the CFLT group were excellent. We observed significant improvement in PaO₂, PaCO₂, forced vital capacity, and forced expiratory volume in the first second of expiration at 6, 12, and 36 months compared with the pretransplantation baseline values.     

Long-term survival despite early loss of graft function after single lung transplantation for pulmonary fibrosis.

We report a patient who received a single, left lung transplantation for idiopathic pulmonary fibrosis. The effect of the graft on pulmonary improvement was only temporary, because the patient developed obliterative bronchiolitis (OB), resulting in complete destruction of the graft. The patient, however, remains alive 6 years after OB was diagnosed, apparently as a consequence of native lung improvement with triple-immunosuppressive medicine. This case is of interest for several reasons: first, it shows that pulmonary fibrosis may respond to intensive immunosuppressive therapy; second, it demonstrates that ventilation scintigraphy is useful in addition to pulmonary function tests in estimating the actual function of the graft after single lung transplantation; and third, it appears that the gradation of bronchiolitis obliterans syndrome (BOS) after single lung transplantation may overestimate the true function of the transplant.     

Unilateral hyperlucent lung: the case for investigation.

Seventeen children with unilateral hyperlucent lungs were referred for investigation. Of the 11 who had a referring diagnosis of possible Macleod's syndrome only two were shown to have post-viral bronchiolitis. Three of the 11 had conditions that required surgical treatment and a further two with brochiectasis were treated medically. To avoid confusion we suggest that Macleod's syndrome is reserved exclusively for children with post-viral bronchiolitis. Radioisotopic regional lung function studies were useful in the investigation of the subjects from three points of view. Firstly, they distinguished children with primary perfusion abnormalities and normal ventilation, secondly, they defined the extent of altered respiratory function, and thirdly, they were able to distinguish compensatory emphysema from congenital lobar emphysema. As bronchography and bronchoscopy may be hazardous in small children with poor respiratory reserve, such regional studies may be useful in indicating which patients do not require further invasive investigation.     

A new method of securing the airway for differential lung ventilation in intensive care

Differential lung ventilation to achieve optimised ventilation for each lung is a procedure rarely used in the intensive care unit, to treat select cases of severe unilateral lung disease in intensive care. However, existing techniques both for securing the airway and ventilating the lungs are challenging and have complications. We present the use of differential lung ventilation in the intensive care setting, securing the airway with a technique not previously described, using endotracheal tubes inserted through a tracheotomy and orally. In the course of 1 month, we treated three patients with unilateral atelectatic and consolidated lungs by differential lung ventilation. The left lung was ventilated through an endotracheal tube inserted into the left main stem bronchus through a tracheotomy. The right lung was ventilated through an endotracheal tube with the cuff positioned immediately under the vocal cord. In patient 1, the diseased lung remained consolidated after 24 h of differential lung ventilation. In the two other patients, the diseased lungs responded to differential lung ventilation by increased compliance and radiographic increased aeration. Differential ventilation of the lungs with this novel technique is feasible and may increase the likelihood of successful treatment of atelectatic lungs refractory to conventional ventilator strategies.     

A potential mechanism by which aspiration of duodenogastric fluid augments the risk for bronchiolitis obliterans syndrome after lung transplantation

ObjectiveAspiration of duodenogastric refluxate may damage the respiratory epithelium of lung allografts in transplant recipients. We sought to define a mechanism by which aspiration of duodenogastric fluid augments the risk of bronchiolitis obliterans syndrome after lung transplant in a murine model.MethodsWe analyzed the immunological effects of acute aspiration of duodenogastric fluid (0.5 mL/kg) on transplant naive (strain DBA/2J) and transplanted mice (strain B6D2F1/J to strain DBA/2J). Serum antibodies to the lung self-antigens (SAgs) K-alpha1 tubulin and collagen-V were determined by enzyme-linked immunosorbent assay. Exosomes were isolated from serum, and immunoblot membranes were probed for antibodies to lung SAgs. Lung sections were assessed for fibrotic burden and obliterative bronchiolitis lesions by histologic and immunohistochemical analyses, including trichrome staining.ResultsTransplanted mice that received duodenogastric fluid developed higher levels of antibodies to the lung SAgs K-alpha1 tubulin and collagen-V and exosomes with lung SAgs on posttransplant days 14 and 28 than transplanted mice with sham aspiration or transplant naive mice (with and without aspiration). All lung allografts demonstrated severe grade A4 rejection on posttransplant day 14, with the highest mean fibrotic burden and mean number of obliterative bronchiolitis-like lesions per microscopic field on day 28 in recipients with aspiration.ConclusionsThis study links aspiration of duodenogastric fluid after lung transplant to higher autoimmune responses to lung SAgs and the release of circulating exosomes with lung SAgs, which together promote sustained immune responses leading to extensive lung parenchymal damage and, ultimately, severe obliterative bronchiolitis—the histologic hallmark of bronchiolitis obliterans syndrome.     

Patterns and significance of CD44 expression in lung allografts.

BACKGROUND: Lung allograft rejection involves the interplay of multiple cellular populations, soluble mediators, and extracellular matrix proteins. The CD44 family of cell surface glycoproteins mediates a variety of cell-cell and cell-matrix interactions including lymphocyte homing to sites of antigenic challenge and fibroblast migration and invasion into extracellular matrix, processes integral to lung allograft rejection. METHODS: We performed immunohistochemical staining for CD44 on biopsies from allograft recipients with differing rejection experiences: Group 1 (n = 5 patients/10 biopsies) never exceeded Grade A1 or B2 acute rejection (AR); Group 2 (n = 7 patients/26 biopsies) had 2 or more episodes of Grade A2 or higher AR and no obliterative bronchiolitis (OB); Group 3 (n = 6 patients/17 biopsies) had clinical and pathologic OB. Nine infected allograft biopsies, 8 near-normal lung sections (non-transplant controls), and 13 non-transplant biopsies showing bronchiolitis obliterans organizing pneumonia (BOOP), organizing diffuse alveolar damage (DAD), or usual interstitial pneumonia (UIP) were also studied. RESULTS: Allograft biopsies demonstrated significantly more CD44 staining among lymphocytes, macrophages, Type II pneumocytes, and respiratory epithelial cells than non-transplant controls, while staining of lymphocytes, macrophages, and Type II pneumocytes did not differ significantly between allograft groups. Fibroblast CD44 staining in Group 3 biopsies significantly exceeded that of controls and Groups 1 and 2, and biopsies with AR and/or OB showed more fibroblast staining than biopsies with BOOP, organizing DAD, or UIP. Alveolar CD44-positive fibroblasts did not predict development of OB, while bronchial CD44-positive fibroblasts were followed in one case by OB. CONCLUSIONS: These findings suggest that CD44 expression is characteristic of graft-infiltrating inflammatory cells and resident parenchymal cells, and may be related to the initiation and evolution of AR and OB.     

End-Stage Respiratory Failure Secondary to Bronchiolitis Obliterans Syndrome Induced by Toxic Epidermal Necrosis,Also Known as Lyell Syndrome: A Case Report

BackgroundStevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but serious dermatologic diseases. They can be associated with systemic manifestations such as bronchiolitis obliterans syndrome (BOS). SJS/TEN-induced BOS is associated with a poor prognosis, and no guidelines exist regarding its management. Several case reports have described the association between SJS/TEN and BOS, with few patients undergoing lung transplantation as a last resort therapy. Unfortunately, in the published reports, none of the transplanted patients were observed for a long period of time after the transplantation; therefore, the long-term mortality as well as the risk of recurrence of BOS could not be inferred from these reports.Case reportWe present the case of a young patient diagnosed with SJS complicated by BOS and end-stage respiratory failure refractory to corticosteroid therapy. She underwent bilateral lung transplantation with an outstanding outcome at 5-year follow-up.ConclusionSJS/TEN-induced BOS might have a favorable evolution and long-term outcomes following lung transplantation. However, prospective studies are needed to confirm this finding.     

Neutrophilic reversible airways dysfunction after liver transplantation: a case report

In the present case report we have described a 46-year-old female patient who underwent a liver transplantation in 1998 for polycystic disease and developed a syndrome of increasing dyspnea, with sputum production and a progressive decline in pulmonary function [forced expiratory volume in one second (FEV(1)) (decreased from 153% predicted to 87% predicted). Further examination revealed an impressive tree in a bud pattern with diffuse peribronchiolar infiltrates on computed axial tomographic scan of the thorax. Sputum cultures remained negative. Bronchoscopic central airway biopsy specimens showed lymphocytic bronchitis; sputum induction showed 92% neutrophils. This condition was similar to the bronchiolitis obliterans syndrome after lung transplantation, although the specific neutrophilic phenotype of bronchiolitis obliterans syndrome has recently been renamed as neutrophilic reversible allograft/airway dysfunction, based on a progressive decline in FEV(1), neutrophilic airway inflammation and its response to neomacrolides. Additional azithromycin treatment resulted in complete recovery in our patient, with normalization of FEV(1) and computed axial tomographic scan of the thorax at 3 months after initiation. This case report suggests that neutrophilic reversible allograft airway dysfunction can no longer be diagnosed only after lung transplantation. Moreover, it demonstrates that this condition is not always related to allograft rejection, but rather may be induced by non-immunologic factors, which remain to be further investigated.     

Lower incidence of bronchiolitis obliterans in pediatric liver-lung transplant recipients with cystic fibrosis

BACKGROUND: Simultaneous liver-lung transplantation is an infrequent but technically feasible procedure in patients with end-stage lung disease and advanced liver disease. We characterize the outcomes of pediatric patients who underwent this procedure at our institution. METHODS: We performed a retrospective, case-control study and reviewed the medical records of all patients referred to our transplant program from its inception. Seven patients were listed for simultaneous liver-lung transplant. The five patients who survived to transplant were matched to 13 controls who underwent isolated bilateral sequential lung transplant for underlying diagnosis, age at time of transplant, gender, and era of transplant. Outcome measures included patient and graft survival, occurrence of bronchiolitis obliterans (BO), and episodes of rejection. RESULTS: Of the five study patients who underwent liver-lung transplant, one died of multiorgan failure 11 days after transplant compared with 9 of 13 controls who died. The median survival for the study patients was 89 months (range, 0-112 months) compared with the controls, who had a median survival of 34 months (range, 0-118 months). The remaining four patients had bronchiolitis obliterans syndrome scores of 0 compared with 5 of 13 control patients (P=0.02). The rate of acute rejection per 100 patient days was 0.012 for the study patients compared with 0.11 for the controls (P=0.025). CONCLUSIONS: Simultaneous liver-lung transplantation is a technically feasible procedure with excellent long-term outcomes. The surviving study subjects remain free from bronchiolitis obliterans syndrome. These results suggest that the transplanted liver may bestow immunologic privilege to the lung allograft.     

Does donor cause of death affect the outcome of lung transplantation?

BACKGROUND: Accumulating evidence suggests that the donor's cause of death may influence posttransplantation allograft function. We conducted a retrospective analysis of our adult lung transplant experience to investigate the influence of donor traumatic brain injury versus nontraumatic brain injury on posttransplantation outcome. METHODS: We retrospectively reviewed donor records and recipient medical charts for 500 consecutive lung transplants performed between July 1988 and December 1999. Recipient follow-up was complete, with a minimum follow-up of 1 year of survival. RESULTS: There were 295 and 205 donors in the traumatic and nontraumatic brain injury groups, respectively. Young male donors predominated in the traumatic brain injury group. Recipients receiving donor lungs from the traumatic and nontraumatic brain injury groups did not differ by age, sex, diagnosis, type of transplant (single-lung versus double-lung) or requirement for pretransplantation mechanical ventilatory assistance. Recipients did not differ in immediate or 24-hour PaO (2)/inspired oxygen ratio, ventilation time, hospital stay, hospital mortality, or overall survival. Recipients of organs from donors who died of traumatic brain injury showed a higher severity and frequency of rejection episodes during the first year after transplantation. Freedoms from bronchiolitis obliterans syndrome at 5 years were 34.5% and 50.8% for recipients of organs from donors who died of traumatic and nontraumatic brain injury, respectively (P =.002). CONCLUSIONS: The cause of donor brain death does not appear to influence early results of lung transplantation. Traumatic brain injury, or some phenomenon associated with it, may predispose a transplanted lung and its recipient toward more severe early rejection episodes and subsequent development of bronchiolitis obliterans syndrome.     

Aktueller Stand der Lungentransplantation

Thirty years after the first successful lung transplantation was performed, it is now a routine procedure for end-stage lung diseases. Significant progress has been made by improvement of surgical techniques, organ procurement and preservation, development of new immunosuppressive protocols, and diagnostic tools to detect rejection, thus, resulting in an increase in 1-year survival to 80%, 3-year survival to 63%, and 5-year survival to 52%. However, only 20% of organ donors have lungs suitable for donation, resulting in increasing deaths on the waiting list. The major problem in the long term remains chronic allograft dysfunction due to bronchiolitis obliterans syndrome. However, quality of life is significantly improved in the majority of patients 5 years after transplantation. In this article, indications, surgical techniques, and results are presented and discussed.     

Noninvasive methods for detection of chronic lung allograft dysfunction in lung transplantation

Lung transplantation (LTx) is the only therapeutic option for end-stage lung diseases. Chronic lung allograft dysfunction (CLAD), which manifests as airflow restriction and/or obstruction, is the primary factor limiting the long-term survival of patients after surgery. According to histopathological and radiographic findings, CLAD comprises two phenotypes, bronchiolitis obliterans syndrome and restrictive allograft syndrome. Half of all lung recipients will develop CLAD in 5 years, and this rate may increase up to 75% 10 years after surgery owing to the paucity in accurate and effective early detection and treatment methods. Recently, many studies have presented noninvasive methods for detecting CLAD and improving diagnosis and intervention. However, the significance of accurately detecting CLAD remains controversial. We reviewed published studies that have presented noninvasive methods for detecting CLAD to highlight the current knowledge on clinical symptoms, spirometry, imaging examinations, and other methods to detect the disease.     

Significance of percutaneous cardiopulmonary bypass support for volume reduction surgery with severe hypercapnia

In patients with reduced respiratory function, lung resection is associated with high risk because separate ventilation is generally needed for safe management. For patients with end-stage emphysema, intraoperative respiratory management is important and particularly difficult because neither incomplete oxygenation nor selective ventilation can be performed, so the operation may be interrupted. In this study, we assess the effectiveness of the percutaneous cardiopulmonary support (PCPS) system for lung volume reduction surgery in patients with severe hypercapnia (arterial carbon dioxide tension >50 mm Hg) and discuss the significance of PCPS for patients who are beyond the standard criteria for lung volume reduction surgery (LVRS). We studied 3 patients with severe hypercapnia due to emphysema who underwent volume reduction surgery. One patient was previously treated surgically for contralateral pneumothorax. All patients had a severe smoking history and were suspected to have fragile lungs. During the operation. PCPS provided sufficient support flow. Intraoperative management using PCPS was easy, and no severe complications were observed. One patient exhibited severe hemodynamic deterioration on postoperative Day 15. Other patients' PaCO2 improved postoperatively. One had a calcification of a femoral artery, but there was no trouble inserting a cannula. Bilateral or unilateral volume reduction surgery was performed under PCPS in patients with end-stage emphysema. We conclude that PCPS is an adjunct to LVRS, useful for intraoperative management of some patients with severe hypercapnea, and the LVRS indications can be extended.     

A Clinical Use of the Kyocera Gyro C1E3 Centrifugal Pump

In patients with reduced respiratory function, lung resection is associated with high risk because separate ventilation is generally needed for safe management. For patients with end-stage emphysema, intraoperative respiratory management is important and particularly difficult because neither incomplete oxygenation nor selective ventilation can be performed, so the operation may be interrupted. In this study, we assess the effectiveness of the percutaneous cardiopulmonary support (PCPS) system for lung volume reduction surgery in patients with severe hypercapnia (arterial carbon dioxide tension >50 mm Hg) and discuss the significance of PCPS for patients who are beyond the standard criteria for lung volume reduction surgery (LVRS). We studied 3 patients with severe hypercapnia due to emphysema who underwent volume reduction surgery. One patient was previously treated surgically for contralateral pneumothorax. All patients had a severe smoking history and were suspected to have fragile lungs. During the operation. PCPS provided sufficient support flow. Intraoperative management using PCPS was easy, and no severe complications were observed. One patient exhibited severe hemodynamic deterioration on postoperative Day 15. Other patients' PaCO2 improved postoperatively. One had a calcification of a femoral artery, but there was no trouble inserting a cannula. Bilateral or unilateral volume reduction surgery was performed under PCPS in patients with end-stage emphysema. We conclude that PCPS is an adjunct to LVRS, useful for intraoperative management of some patients with severe hypercapnea, and the LVRS indications can be extended.     

Chlamydia pneumoniae infection after lung transplantation.

BACKGROUND: Chlamydia pneumoniae is established as a common agent of acute respiratory tract infection and has been implicated in the pathogenesis of asthma and chronic obstructive pulmonary disease. Airway disease is a prominent cause of morbidity and mortality after lung transplantation. We investigated the role of C pneumoniae as a pulmonary pathogen after lung transplantation. METHODS: Eighty lung transplant recipients underwent 232 bronchoscopies with bronchoalveolar lavage with or without transbronchial lung biopsy during 1 year for surveillance of rejection and infection, or where clinically indicated. RESULTS: C pneumoniae was detected using nested polymerase chain reaction in 9 of 36 (25%) recipients studied within 30 days of lung transplantation, 3 of whom remained positive on repeat lavage and died from airway disease in the first year post-operatively. By comparison, all 27 recipients with negative lavage survived >1 year. Lavage was positive for C pneumoniae in 18 of 71 (25%) recipients studied >30 days after lung transplantation, 5 of whom had pneumonia and 8 of whom had bronchiolitis obliterans syndrome. Eleven also had acute pulmonary allograft rejection. CONCLUSIONS: Persistent infection with C pneumoniae (whether donor-derived, de novo or re-activated) appears deleterious to pulmonary allograft function and is associated with early mortality, rejection and bronchiolitis obliterans syndrome after lung transplantation. A trial of empiric antibiotic therapy for C pneumoniae may therefore be warranted in the attempt to prevent progressive inflammatory airway disease.