Lung transplant infection

Lung transplantation has become an accepted therapeutic procedure for the treatment of end‐stage pulmonary parenchymal and vascular disease. Despite improved survival rates over the decades, lung transplant recipients have lower survival rates than other solid organ transplant recipients. The morbidity and mortality following lung transplantation is largely due to infection‐ and rejection‐related complications. This article will review the common infections that develop in the lung transplant recipient, including the general risk factors for infection in this population, and the most frequent bacterial, viral, fungal and other less frequent opportunistic infections. The epidemiology, diagnosis, prophylaxis, treatment and outcomes for the different microbial pathogens will be reviewed. The effects of infection on lung transplant rejection will also be discussed.     

Laryngeal cancer: long-term follow-up of respiratory functions after laryngectomy

Pulmonary function of 31 heavy smokers with laryngeal cancer was evaluated before and during the 1st year after total (n = 21) and conservative (n = 10) laryngectomy. 2 of them died because of recurrences, 1 for bronchopulmonary complications. Long-lasting hoarseness was the only presenting symptom in all patients. Preoperative lung function data and mucociliary clearance were consistent with a coexisting chronic obstructive lung disease in most subjects and was probably due to smoking. No differences were observed comparing pre- and postoperative data in the 10 conservative laryngectomy patients. On the contrary, the total-laryngectomy patients showed a progressive impairment of bronchial obstruction and bacteriological infection of the trachea during the 1st year after the operation. An impressive increase in mucociliary clearance rates has been observed 2 months after total laryngectomy during the postoperative hypersecretory phase. the obtained data allow us to hypothesize that when clinical conditions of laryngectomized patients in whom local or distant recurrences have been excluded deteriorate, this is related to a progressive bronchial obstruction at any level of the bronchial tree due to descending bacterial infection of the airways. To our knowledge this is the only work demonstrating that total laryngectomized patients need a complete pre- and postoperative evaluation of lung function, airway dynamics, mucociliary function and tracheal bacteriology for long-term prognosis and treatment.     

Bronchiectasis: a cause of pulmonary symptoms in heroin addicts.

Extensive and severe bronchiectasis was found in 7 heroin-addicted individuals with pulmonary symptoms whose chest roentgenograms were not suggestive of severe airway disease. Abnormalities consisted of varicose and cylindrical alterations. Pulmonary function tests revealed airflow obstruction, decreased lung volumes, and diffusion capacity impairment. Arterial blood gas analysis demonstrated mild hypoxemia in all patients and chronic hypocapnia in 4. Serial pulmonary function tests in 2 patients revealed only modest improvement in the degree of airflow obstruction. The occurence of bronchiectasis appeared to be related to episodes of heroin-induced pulmonary edema and infection.     

Lung function associated with histologically diagnosed acute lung rejection and pulmonary infection in heart-lung transplant patients

A group of 34 heart-lung transplant patients were studied with serial pulmonary function measurements, chest radiographs, and transbronchial biopsies from the time of surgery. These investigations were carried out routinely at 3 and 6 months and then annually after transplantation as well as on clinical suspicion of acute lung rejection or infection. A total of 61 transbronchial biopsies and concurrent lung function and chest radiographs were obtained. Of the biopsies, 30 (49.2%) showed histologic evidence of lung rejection, 12 (19.7%) demonstrated various opportunistic infections, and 19 (31.1%) were normal. Compared to during episodes of normal biopsies, FEV1 decreased significantly with lung rejection (p less than 0.001) and with infection (p less than 0.01). Vital capacity (VC) and DLCO also fell with these acute lung complications. Using histologic diagnosis as a standard, lung function testing had a sensitivity of 86% in detecting lung rejection in the first 3 months postoperation and 75% in the subsequent period. Its sensitivity for detecting lung infection was 75%. Although not distinguishing between these two complications, lung function had a specificity of 84% for detecting occurrence of an acute lung complication. Chest radiographs, although of similar sensitivity in the first 3 months postsurgery, had a sensitivity of only 19% for rejection in subsequent months and 58% for infection. Its specificity was 100%. Lung function testing changes in a predictable fashion with lung rejection and infection, offers an improvement over chest radiographs, and provides a quantitative measurement to aid the decision of when to undertake transbronchial lung biopsy.     

Acute exacerbations and respiratory failure in chronic obstructive pulmonary disease

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) describe the phenomenon of sudden worsening in airway function and respiratory symptoms in patients with COPD. These exacerbations can range from self-limited diseases to episodes of florid respiratory failure requiring mechanical ventilation. The average patient with COPD experiences two such episodes annually, and they account for significant consumption of health care resources. Although bacterial infections are the most common causes of AECOPD, viral infections and environmental stresses are also implicated. AECOPD episodes can be triggered or complicated by other comorbidities, such as heart disease, other lung diseases (e.g., pulmonary emboli, aspiration, pneumothorax), or systemic processes. Pharmacologic management includes bronchodilators, corticosteroids, and antibiotics in most patients. Oxygen, physical therapy, mucolytics, and airway clearance devices may be useful in selected patients. In hypercapneic respiratory failure, noninvasive positive pressure ventilation may allow time for other therapies to work and thus avoid endotracheal intubation. If the patient requires invasive mechanical ventilation, the focus should be on avoiding ventilator-induced lung injury and minimizing intrinsic positive end-expiratory pressure. These may require limiting ventilation and "permissive hypercapnia." Although mild episodes of AECOPD are generally reversible, more severe forms of respiratory failure are associated with a substantial mortality and a prolonged period of disability in survivors.     

Pulmonary complications in patients with antibody deficiency

ObjectiveThe aim of this study was to evaluate pulmonary complications in patients with primary antibody deficiency (X-linked agammaglobulinaemia [XLA] and common variable immunodeficiency [CVID]).MethodsThirty patients over six years of age regularly followed in a reference out-patient clinic on primary immunodeficiency were studied. All of them have been treated with intravenous immunoglobulin (IVIG) replacement therapy. Pulmonary complications were evaluated analysing clinical data (medical records review), lung function test (spirometry) and pulmonary imaging (chest computed tomography [CCT]).ResultsPatients with normal CCT (N=14) and those with abnormal CCT (N=16) have shown no differences regarding the age at onset of symptoms, age of diagnosis, and duration of IVIG treatment. The mean number of pneumonia episodes before IVIG replacement was significantly higher among patients with abnormal CCT (4 vs 7 episodes, p=0.008). CCT abnormalities observed in 16 patients were: bronchiectasis (12/16); peribronchial thickening (3/16); air trapping (5/16); lung volume reduction (4/16); atelectasis (2/16), follicular bronchiolitis and ground-glass abnormality (2/16) and parenchyma nodule (1/16). Lung function tests showed ventilatory disturbance in 18/30: obstructive pattern in 38.8%, restrictive pattern in 44.4%, and mix pattern in 16.7%. There were no significant differences in lung function between those with and without CCT abnormalities. Negative significant correlations were observed between lung function and number of episodes of pneumonia. Chronic persistent cough was associated with a reduction in lung function.ConclusionsPulmonary complications are not rare in patients with antibody deficiencies and they must be monitored.     

Comparison of pulmonary diseases in common variable immunodeficiency and X‐linked agammaglobulinaemia

Background and objective: Pulmonary disease is the most common complication in patients with common variable immunodeficiency (CVID) or X‐linked agammaglobulinaemia (XLA). Pulmonary disease may progress despite immunoglobulin replacement therapy. In this study pulmonary complications were compared in patients with CVID or XLA. Methods: Pulmonary complications were evaluated in 115 patients (76 with CVID and 39 with XLA) by reviewing hospital records of chest infections, pulmonary function tests and high‐resolution CT scans. Results: Thirty‐two patients with XLA (82%) presented with 59 episodes of pneumonia before diagnosis, whereas 15 patients (38.4%) experienced pneumonia after immunoglobulin replacement therapy (1.67 vs 0.45 episodes per patient per year). Among the CVID patients, 196 episodes of pneumonia were documented in 59 patients (77.6%) before diagnosis, while 36 patients (47.3%) experienced pneumonia after therapy (1.11 vs 0.58 episodes of pneumonia per patient per year). Forty‐seven (41%) patients (38 with CVID and 9 with XLA) developed chronic lung disease. The CVID patients developed more complications, including bronchiectasis and lymphoid interstitial pneumonitis, than the XLA patients. Conclusions: Patients with CVID had a greater likelihood of developing lung disease, possibly due to delayed diagnosis and immune dysregulation, as compared with XLA patients. Early diagnosis of patients with primary antibody deficiencies and adequate i.v. immunoglobulin replacement therapy substantially reduces the number of pulmonary infections. However, CVID patients are prone to progression of lung disease despite optimal immunoglobulin therapy because of the nature of the disease. This important issue should be addressed in further studies.     

Heart-lung transplantation: an overview

Heart-lung transplantation is in a state of evolution, but for selected patients with end-stage cardiopulmonary and pulmonary disease, it can offer long-term rehabilitation. In the 8 years since heart-lung transplantation was begun at Stanford, much experience has accrued and significant improvements have been made. Advances that have made heart-lung transplantation feasible include better immunosuppression, particularly the triple-drug protocol of cyclosporine, azathioprine, and corticosteroids which decreases the incidence of obliterative bronchiolitis. Techniques of improved lung preservation have made distal donor procurement a reality, and increasing numbers of lung and heart-lung transplantations are now being performed. More importantly, better recipient and donor selection has occurred such that the perioperative mortality has been reduced from 35 to 16 per cent. Currently, the major threat facing survivors of heart-lung transplantation is the insidious development of restrictive airway disease. Our impression is that the development of obliterative bronchiolitis results from repeated rejection episodes or possibly an injury mechanism following severe viral pneumonia. The common pathway seems to be repeated injury and repair mechanism, with the end-stage being obliterative bronchiolitis by scar formation. As suggested, the injury mechanism is probably that of repeated or chronic rejection. To further support the hypothesis of an immunerelated etiology, obliterative bronchiolitis has occurred in recipients of bone marrow transplants if they develop graft-versus-host disease. In an attempt to ameliorate the effects of rejection on airway function, we have increased our maintenance immunosuppression by adding azathioprine. Consequently, patients with early obliterative bronchiolitis on enhanced immunosuppression have had stabilization of the airway disease, and we have noted a significant reduction in the occurrence of obliterative bronchiolitis from 62 per cent in Group 1 patients to 20 per cent in Group 2 patients. Since obliterative bronchiolitis may be reversed by early recognition and treatment of rejection, we have aggressively used bronchoscopy with transbronchial lung biopsy and bronchoalveolar lavage for surveillance of both rejection and infection in our recent patients. Open lung biopsy has not been used since 1986 to diagnose rejection, and we are encouraged that bronchoscopic surveillance is sensitive and effective. The primary goal of the bronchoscopic evaluation protocol was to monitor the patients closely and to treat both rejection and infection early and effectively. Concurrently, we are also measuring pulmonary function parameters, which includes FEV1, FEF 25-75, PaO2, total lung capacities, and profusion gradients. The desired outcome was the maintenance of normal airway dynamics by reversing airway disease at a reversible stage.(ABSTRACT TRUNCATED AT 400 WORDS)     

Infections and airway inflammation in chronic obstructive pulmonary disease severe exacerbations

RATIONALE: Severe exacerbations of chronic obstructive pulmonary disease (COPD) are major causes of health care costs mostly related to hospitalization. The role of infections in COPD exacerbations is controversial. OBJECTIVES: We investigated whether COPD exacerbations requiring hospitalization are associated with viral and/or bacterial infection and evaluated relationships among infection, exacerbation severity, assessed by reduction of FEV1, and specific patterns of airway inflammation. METHODS: We examined 64 patients with COPD when hospitalized for exacerbations, and when in stable convalescence. We measured lung function, blood gases, and exhaled nitric oxide, and examined sputum for inflammation and for viral and bacterial infection. RESULTS: Exacerbations were associated with impaired lung function (p < 0.01) and increased sputum neutrophilia (p < 0.001). Viral and/or bacterial infection was detected in 78% of exacerbations: viruses in 48.4% (6.2% when stable, p < 0.001) and bacteria in 54.7% (37.5% when stable, p = 0.08). Patients with infectious exacerbations (29.7% bacterial, 23.4% viral, 25% viral/bacterial coinfection) had longer hospitalizations (p < 0.02) and greater impairment of several measures of lung function (all p < 0.05) than those with noninfectious exacerbations. Patients with exacerbations with coinfection had more marked lung function impairment (p < 0.02) and longer hospitalizations (p = 0.001). Sputum neutrophils were increased in all exacerbations (p < 0.001) and were related to their severity (p < 0.001), independently of the association with viral or bacterial infections; sputum eosinophils were increased during (p < 0.001) virus-associated exacerbations. CONCLUSIONS: Respiratory infections are associated with the majority of COPD exacerbations and their severity, especially those with viral/bacterial coinfection. Airway neutrophilia is related to exacerbation severity regardless of viral and/or bacterial infections. Eosinophilia is a good predictor of viral exacerbations.     

The radiographic appearances of infection and acute rejection of the lung after heart-lung transplantation

Thirty-two patients underwent combined heart and lung transplantation at Papworth Hospital between 1984 and 1987. The clinical and physiologic observations made at the time of episodes of infection and rejection together with the histopathology of lung tissue obtained by transbronchial lung biopsy were compared with pre- and postepisode chest radiographs. There were 45 episodes of rejection in 20 patients: 23 episodes during the first month after transplantation, and 22 after 1 month. Twenty-six episodes of infection occurred in 15 patients. The causative organisms included Aspergillus fumigatus, cytomegalovirus (CMV), herpes simplex, Pneumocystis carinii, and Staphylococcus aureus. When an abnormal chest radiograph is common during the first month after transplantation during acute rejection (74%), it may alternatively be due to lung infection (most commonly CMV pneumonitis). The chest radiograph during this period provides a useful indication for transbronchial biopsy and bronchial lavage. The chest radiograph is abnormal in the minority (23%) of episodes of rejection occurring later than 1 month after transplantation. Pulmonary function tests (FEV1 and VC) offered a more useful indication for transbronchial biopsy during this period.     

Increased lung clearance of 99mTcDTPA in allograft lung rejection. The Paris-Sud Lung Transplant Group.

To investigate whether lung 99mTc-DTPA clearance is altered during allograft lung rejection, a group of four double lung and 24 heart-lung transplant patients was studied using serial measurement of the clearance rate of aerosolized 99mTc-DTPA (DTPA-Cl), in association with pulmonary function tests, bronchoalveolar lavage, and transbronchial lung biopsies. Using histologic diagnosis as a standard, we compared 56 episodes with normal lung histology to 32 episodes with allograft lung rejection. A control group of 20 healthy nonsmokers was used to define normal DTPA-Cl. In patients with normal lung histology, DTPA-Cl was higher than in control subjects (2.62 +/- 0.25 versus 1.20 +/- 0.12 %/min; p less than 0.001). In the episodes of allograft lung rejection, DTPA-Cl increased to 3.65 +/- 0.41 %/min (p less than 0.02) as compared with episodes of normal lung histology. The change in DTPA-Cl during allograft lung rejection was correlated (r = 0.3, p less than 0.01) with the increased percentage of lymphocytes in bronchoalveolar lavage (27.8 +/- 3.5% in rejection versus 19.9 +/- 2.2% in normal histology; p less than 0.02). Sensitivity and specificity of DTPA-Cl measurement in detecting lung rejection were 69 and 82%, respectively, versus 45 and 85% for FEV1 measurement. These results suggest that DTPA-Cl monitoring could be used in conjunction with pulmonary function testing as a noninvasive approach for the detection of lung rejection.     

Legionella infections in cyclosporine-immunosuppressed cardiac transplants

Pulmonary infections from bacterial or viral agents, as well as rare infectious agents, such as Toxoplasma gondii, Aspergillus, and Pneumocystis carinii, have been a bane to the clinician in charge of the care of transplant patients. One such opportunistic Organism, Legionella pneumophila, was responsible for four episodes of infection in three of our patients who survived due to better management of immunosuppression, together with aggressive therapy and early diagnosis of the infectious complications.     

Infectious complications following isolated lung transplantation.

STUDY OBJECTIVE: To ascertain the incidence, types, morbidity, and mortality of infectious episodes in isolated lung transplant recipients. DESIGN: Retrospective chart review of patients who have undergone transplants over a six-year period in one institution. PATIENTS: Twenty-three single and 17 double lung transplants followed up between 2 and 68 months. RESULTS: Fifty-one episodes of infection occurred in the group with a slight predominance in the double lung transplants. The 32 episodes of bacterial infection constituted the largest group of infection and more than half of these were pneumonias. Organisms identified were predominantly Gram negative. While bacterial processes made up the bulk of infections, fatalities were rare. Viral and fungal infections were less common, but more often fatal. Of six cases of viral pneumonitis, two were fatal; two of five cases of invasive fungal infection were also fatal. Overall, six patients died of infection. CONCLUSION: Our findings support previous reports from heart-lung centers documenting a high rate of infectious complications, particularly pneumonia, in recipients of lung grafts. In our experience, bacterial infections are the most common (two of three infections), but have the lowest mortality. Efforts should be directed toward establishing effective prophylaxis programs and early detection of infection.     

Pulmonary complications of bone marrow transplantation

Bone marrow transplantation (BMT) for hematologic disorders is potentially curative in selected persons. These patients may be immunocompromised for months after engraftment as a consequence of chemotherapy, irradiation, acute and chronic graft-vs-host disease (GVHD), and maturing recipient marrow. Pulmonary complications commonly occur during the early and late periods after BMT and are associated with significant morbidity and mortality. The leading early-onset complication is interstitial pneumonitis, most commonly associated with cytomegalovirus infection but also related to possible toxicities from chemotherapy and irradiation. Major late-onset problems include bacterial sinopulmonary infections and obstructive airway disease thought to be associated with chronic GVHD. The exact mechanisms of lung injury are probably quite complex, and unfortunately, often cause irreversible pulmonary disease, even in the patient who has had successful transplantation. Antimicrobial prophylaxis, modified chemotherapy and irradiation dosages, and antiviral immunization have been shown to reduce the incidence of early-onset pulmonary problems. Early recognition and treatment of late-onset problems will, it is hoped, minimize respiratory limitations.     

Airway effects of marijuana, cocaine, and other inhaled illicit agents

Several substances besides tobacco are inhaled for recreational purposes, including marijuana, crack cocaine, amyl and butyl nitrites, heroin, methamphetamine, and phencyclidine. Abuse of most of these inhaled substances has risen in recent years, thereby increasing concern about potential pulmonary and other medical complications. Regular marijuana use can lead to extensive airway injury and alterations in the structure and function of alveolar macrophages, potentially predisposing to pulmonary infection and respiratory cancer. Crack cocaine use can lead to a variety of acute pulmonary complications, including severe exacerbations of asthma and an acute lung injury syndrome associated with a broad spectrum of histopathologic changes ("crack lung"). Habitual cocaine smoking may also produce more subtle long-term pulmonary consequences due to chronic alveolar epithelial and microvascular lung injury. Heroin inhalation can induce severe and even fatal exacerbations of asthma. Pulmonary consequences of inhaled amyl and butyl nitrites, crystalline methamphetamine (ice), and phencyclidine have been less well documented.     

Lung function abnormalities in HIV‐infected adults and children

Despite the advent of antiretroviral therapy (ART), the human immunodeficiency virus (HIV) epidemic remains a global health crisis with a high burden of respiratory disease among infected persons. While the early complications of the epidemic were dominated by opportunistic infections, improved survival has led to the emergence of non‐infectious conditions that are associated with chronic respiratory symptoms and pulmonary disability. Obstructive ventilatory defects and reduced diffusing capacity are common findings in adults, and the association between HIV and chronic obstructive pulmonary disease is increasingly recognized. There is synergism between viral factors, opportunistic infections, conventional influences like tobacco smoke and biomass fuel exposure, and potentially, the immunological effects of ART on the development of HIV‐associated chronic obstructive lung disease. Pulmonary function data for HIV‐infected infants and children are scarce, but shows that bronchiectasis and obliterative bronchiolitis with severe airflow limitation are major problems, particularly in the developing world. However, studies from these regions are sorely lacking. There is thus a major unmet need to understand the influences of chronic HIV infection on the lung in both adults and children, and to devise strategies to manage and prevent these diseases in HIV‐infected individuals. It is important for clinicians working with HIV‐infected individuals to have an appreciation of their effects on measurements of lung function. This review therefore summarizes the lung function abnormalities described in HIV‐positive adults and children, with an emphasis on obstructive lung disease, and examines potential pathogenic links between HIV and the development of chronic pulmonary disability.     

Pulmonary Function in Scleroderma

Pulmonary function tests were performed in 45 patients with scleroderma. Thirteen patients (29%) were found to have restrictive disease, 12 patients (27%) were found to have obstructive disease, and 19 patients (42%) had small airway disease (SAD). Smoking did not seem to be a factor underlying either obstructive or small airway disease in these patients. A low diffusing capacity was most common in patients with restrictive disease and rarely the only abnormality in pulmonary function. SAD was usually found in patients who had normal chest radiographs and no pulmonary symptoms and was often the only abnormality. SAD is therefore an early and sensitive indicator of pulmonary involvement in scleroderma.     

Patterns of airway involvement in inflammatory bowel diseases

Extraintestinal manifestations occur commonly in inflammatory bowel diseases(IBD). Pulmonary manifestations(PM) of IBD may be divided in airway disorders, interstitial lung disorders, serositis, pulmonary vasculitis, necrobiotic nodules, drug-induced lung disease, thromboembolic lung disease and enteropulmonary fistulas. Pulmonary involvement may often be asymptomatic and detected solely on the basis of abnormal screening tests. The common embryonic origin of the intestine and the lungs from the primitive foregut, the co-existence of mucosa associated lymphoid tissue in both organs, autoimmunity, smoking and bacterial translocation from the colon to the lungs may all be involved in the pathogenesis of PM in IBD. PM are mainly detected by pulmonary function tests and highresolution computed tomography. This review will focus on the involvement of the airways in the context of IBD, especially stenoses of the large airways, tracheo-bronchitis, bronchiectasis, bronchitis, mucoid impaction, bronchial granulomas, bronchiolitis, bronchiolitis obliterans syndrome and the co-existence of IBD with asthma, chronic obstructive pulmonary disease, sarcoidosis and a1-antitrypsin deficiency.     

慢性阻塞性肺疾病稳定期下呼吸道细菌定植状况

慢性阻塞性肺疾病（COPD）是严重危害人类健康的一种疾病,感染是COPD发病和加剧的重要因素之一,稳定期患者下呼吸道存在细菌定植,主要是嗜血杆菌属、肺炎链球菌和卡他莫拉菌,细菌定植的存在与气道炎症、肺功能的降低有关,并且当细菌负荷量超过阈值时就会产生足够严重的炎症反应,从而诱发加重期的临床症状,使疾病迅速进展。