Is bronchoscopic lung biopsy helpful in the management of patients with diffuse lung disease?

Few studies have evaluated how the results of bronchoscopic lung biopsy (BLB) affect clinical management. The objective of the present study was to evaluate the clinical usefulness of BLB in the overall management of patients with diffuse pulmonary diseases. The study was a retrospective analysis of patients who underwent fluoroscopy-guided BLB over a 2-yr period. Patients whose biopsy was of a lung mass or single dominant lung nodule were excluded. The usefulness of BLB was assessed to determine whether the results affected the clinical management of these patients. During the study period, 603 patients underwent 651 BLB procedures. The results of BLB were clinically helpful in 494 (75.9%) out of 651 procedures. No diagnostic abnormality was identified in 107 (16.4%) out of the 651 biopsy procedures. This finding was clinically helpful in 59 (55.1%) out of 107 procedures, as the results excluded specific processes suspected before BLB. In 52 procedures (8% of all BLB), no lung parenchyma was obtained. In conclusion, bronchoscopic lung biopsy is a clinically useful test in approximately 75% of procedures. In the 25% of bronchoscopic lung biopsies that were clinically unhelpful, the reason for failure in approximately one-third of patients was the failure of the procedure to obtain an adequate quantity of lung parenchyma for a meaningful histological analysis.

Aerosol granulocyte-macrophage colony-stimulating factor for pulmonary alveolar proteinosis.

Recently, granulocyte-macrophage colony-stimulating factor (GM-CSF) auto-antibodies have been found in many patients with pulmonary alveolar proteinosis (PAP). The present study reports a retrospective case series of patients who used aerosolised GM-CSF in the treatment of idiopathic PAP. Between 1999 and 2003, 12 patients elected to receive aerosolised GM-CSF (250 microg b.i.d. every other week) in lieu of whole-lung lavage or observation. Patient characteristics, pulmonary function tests, arterial blood gas analysis, laboratory values and chest radiographs were extracted from the patient's medical records. Of the six patients tested, all had GM-CSF neutralising antibodies. Additionally, abnormalities in GM-CSF gene expression (one patient), receptor expression (two patients) and ability to upregulate adhesion molecules (one patient) were found. All patients except one had a positive response (mean improvements in arterial oxygen tension, alveolar-arterial oxygen gradient, carbon monoxide diffusing capacity of the lung and forced vital capacity were 17.1 mmHg, 18.4 mmHg, 16.6% pred and 13.5% pred, respectively). Two patients made a complete recovery and were disease free 1 and 2 yrs after discontinuing treatment. Four patients showed complete response to both the initial course or when treated again for recurrence after discontinuation of treatment. One patient required dose escalation (500 microg b.i.d.) with complete response. GM-CSF was well tolerated without late toxicity after median (range) follow-up of 30.5 (3-68) months. In conclusion, aerosolised granulocyte-macrophage colony-stimulating factor is safe and effective in treating pulmonary alveolar proteinosis providing an alternative to whole-lung lavage or subcutaneous granulocyte-macrophage colony-stimulating factor.

Peri-engraftment respiratory distress syndrome during autologous hematopoietic stem cell transplantation.

From 1987 to 1998, 19 of 416 patients (4.6%) who underwent autologous hematopoietic stem cell transplantation experienced peri-engraftment (within 5 days of neutrophil recovery) respiratory distress syndrome (PERDS) not attributable to infection, fluid overload, or cardiac dysfunction. The median time from stem cell infusion to onset of PERDS was 11 days (range 4-25). Risk of PERDS or its outcome was not predicted by any pre- or peri-transplant clinical or laboratory feature. The respective median white blood cell and platelet counts at first symptoms were 1.3 x 10(9)/l and 25 x 10(9)/l. No patients had an infectious etiology by bronchoalveolar lavage. Six of the 19 patients had alveolar hemorrhage, which was significantly correlated with high neutrophil count. PERDS was directly implicated in four deaths (21%). Eleven patients received high-dose corticosteroid therapy, including five of the six who required mechanical ventilation. Ten of these patients experienced clinical improvement, which occurred within 24 h in five. The rapid response to corticosteroid treatment and the fact that such therapy was delayed until after intubation in all the mechanically ventilated cases point to a therapeutic benefit.

Role of bronchoscopy in modern medical intensive care unit.

This article gives a broad overview of the increasingly important applications of bronchoscopy, flexible (FOB) and rigid (RB), in a modern medical intensive care unit. Special emphasis is made to bronchoscopy use in mechanically ventilated patients. Therapies such as endobronchial stenting and Nd:YAG laser are being used to improve respiratory failure and facilitate weaning from mechanical ventilation. Practical applications of recent advancements in technology (endobronchial stenting, laser therapy, and so forth), the increasing use of rigid bronchoscopy, and the new generation of flexible bronchoscopes like battery bronchoscopes, and ultra-thin bronchoscopes, are also discussed. The risks, potential benefits, complications, and suggested technique of performing bronchoscopy in mechanically ventilated patients are reviewed.

Tracheobronchial amyloidosis.

OBJECTIVE: To evaluate the presentation and clinical course of patients with tracheobronchial amyloidosis. PATIENTS AND METHODS: We retrospectively reviewed the records of all patients with biopsy-proven tracheobronchial amyloidosis who were evaluated at the Mayo Clinic in Rochester, Minn, between 1973 and 1999. All relevant information, such as clinical, historical, demographic, laboratory, and histological data, was examined. RESULTS: Tracheobronchial amyloidosis was diagnosed in 17 patients (9 women and 8 men), with a mean age of 56.6 years. The most common symptoms at presentation were dyspnea, cough, hemoptysis, and hoarseness. None of the 14 patients who underwent investigation for systemic amyloidosis had any evidence of disease outside the tracheobronchial system except for a man in whom multiple myeloma had been diagnosed 3 years before the development of respiratory disease. Treatment of tracheobronchial amyloidosis consisted of laser or forceps resection, external radiation, systemic therapy, or observation. Two patients died of complications directly related to their disease. CONCLUSIONS: Patients presenting with tracheobronchial amyloidosis have symptoms similar to those caused by various airway disorders. Tracheobronchial amyloidosis is not typically associated with systemic amyloidosis or pulmonary parenchymal involvement. It often recurs and despite repeated attempts with bronchoscopic techniques, airway compromise remains a major problem.

Varicella-zoster virus detection by polymerase chain reaction using bronchoalveolar lavage specimens.

We report the use of polymerase chain reaction (PCR) techniques from a bronchoalveolar lavage (BAL) specimen for the successful early diagnosis in a case of atypical but severe varicella-zoster virus (VZV) pneumonitis. Atypical presentations of disseminated VZV frequently prolong the time required for accurate diagnosis, resulting in increased morbidity, or mortality. Although further investigation is necessary to determine the sensitivity and positive predictive value of this test, PCR analysis of bronchoscopic specimens may expedite the diagnosis of disseminated VZV.

The role of anticholinergics in bronchoscopy. A randomized clinical trial.

BACKGROUND: Anticholinergic medications have been utilized frequently prior to bronchoscopy and are thought to facilitate the drying of secretions to limit the amount of required topical anesthetic on the airway mucosa, prevent cardiac arrhythmias during the procedure, and increase patient comfort. OBJECTIVE: To determine if atropine or glycopyrrolate, two anticholinergic agents utilized most frequently in this setting, have any significant role for this purpose. DESIGN: Double-blind, placebo-controlled study, in which patients were randomly selected to receive atropine (0.01 mg/kg body weight, IM injection), glycopyrrolate (0.005 mg/kg, IM injection), or saline solution placebo (approximately 2 mL, IM injection) 15 to 45 min prior to being sedated with midazolam until judged to be lightly sedated. SETTING: A large academic teaching hospital in the midwestern United States. PARTICIPANTS: Two hundred seventeen outpatients referred for bronchoscopy who satisfied inclusion and exclusion criteria. MEASUREMENTS AND RESULTS: Using a modified visual analog scale (0 to 100 mm), the bronchoscopist and the nurse anesthetist estimated the antisialagogic effect, effectiveness in cough suppression, and overall patient comfort during the procedure. The patients completed a similar questionnaire after recovering from the procedure. Patients were also monitored for complications (cardiac arrhythmias, oxygen desaturation, hypertension, wheezing, or coughing severe enough to curtail the procedure). There was no significant difference found among atropine, glycopyrrolate, and placebo for the primary end point of secretion control. In addition, there was no difference found between either medication and placebo for effectiveness of cough suppression, amount of topical anesthetic used, complication rates, or overall patient comfort. CONCLUSION: The use of anticholinergic agents prior to bronchoscopy did not affect performance of bronchoscopy or complication rates, and there was no appreciable benefit from the resultant reduction in airway secretions in a population of patients receiving concurrent sedation with benzodiazepines.

Alpha1-antitrypsin deficiency and inflammatory bowel diseases.

OBJECTIVE: To evaluate a possible etiologic role of alpha1-antitrypsin deficiency (alpha1AD), most frequently caused by a Z allele mutation, in ulcerative colitis (UC) and Crohn disease (CD). PATIENTS AND METHODS: This retrospective study included 10 patients diagnosed with and/or treated for inflammatory bowel disease (IBD) between 1976 and 1997 and identified from the Mayo Clinic Medical Index System. All 10 patients had either alpha1AD and CD or alpha1AD and UC. The alpha1-antitrypsin (alpha1AT) types and levels were determined with isoelectric focusing testing. The allele types, representing genotypes, were designated PiZZ (or ZZ) for homozygotes and PiMZ (or MZ) for heterozygotes. RESULTS: Seven patients had UC: 4 were genotype ZZ and 3 MZ. Four of these 7 patients had emphysema, 2 had asthma, and 1 had chronic bronchitis. Five were cigarette smokers, but only 1 had smoked coincident with activity of her UC. Two of the UC patients never smoked, and 1 of these 2 had asthma. Three of the 10 patients had CD, 2 genotype ZZ and 1 MZ. Two of the 3 patients were long-term cigarette smokers, and both had emphysema. Nine of the 10 patients with UC and alpha1AD required surgery. CONCLUSIONS: The need for surgery in patients with UC and alpha1-AD may point to a unique phenotypic subgroup of patients with alpha1AD and severe UC. Further studies are required to substantiate the etiologic role of alpha1AD in IBD. Our observations, if confirmed by future studies, suggest that in patients with both IBD and chronic obstructive pulmonary disease, alpha1AD testing should be considered.

Advances in bronchoscopic procedures.

Bronchoscopy is currently the most commonly employed invasive procedure in the practice of pulmonary medicine. Both the rigid and flexible bronchoscopes are used to diagnose and treat various pulmonary disorders. The main diagnostic indications include pulmonary involvement by neoplasms, infections, diffuse lung diseases, and airway problems. Bronchoscopic needle aspiration remains an underutilized technique in the staging of lung cancer. Newer techniques such as bronchoscopic ultrasound appear promising and may lead to improved diagnostic yield from bronchoscopic procedures. The bronchoscope is used in application of laser therapy, brachytherapy, electrocautery, cryotherapy, placement of airway stents, and balloon dilatation to relieve airway obstruction caused by malignant and benign airway lesions.

Therapeutic bronchoscopy in broncholithiasis.

Bronchoscopy is considered the most important diagnostic test for broncholithiasis. However, its role in the treatment of broncholithiasis in a large group of patients has not been studied. To evaluate the therapeutic role of bronchoscopy, we retrospectively reviewed the clinical data of patients with broncholithiasis who also underwent bronchoscopy at Mayo Clinic. Bronchoscopy revealed 127 broncholiths (free or partly eroded calcified material in the airway lumen) in 95 patients (49 men and 46 women) evaluated between 1954 and 1994. Bronchoscopic removal of 71 (56%) broncholiths was attempted in 48 patients (50.5%) during 61 bronchoscopy sessions. Forty-eight of the broncholiths selected for removal were partly eroding into the tracheobronchial lumen and 23 were free. Forty-eight percent (23 of 48) of the partly eroding broncholiths were successfully removed bronchoscopically, with a greater percentage removed with the rigid bronchoscope (67%) than with the flexible bronchoscope (30%). All free broncholiths were completely extracted regardless of the type of bronchoscope used. Complications occurred in only two patients (4% of the bronchoscopic broncholithectomy group), both with partially eroded broncholiths, and consisted of hemorrhage in one patient requiring thoracotomy and acute dyspnea in another patient, caused by a loose broncholith lodged in the trachea. We conclude that flexible and/or rigid bronchoscopic extraction of partly eroded or free broncholiths in the tracheobronchial tree can be considered safe and effective.

Pulmonary arteriovenous fistulas: Mayo Clinic experience, 1982-1997.

OBJECTIVE: To describe the results of analysis of clinical, physiologic, diagnostic, and therapeutic aspects and complications in patients with pulmonary arteriovenous fistulas (PAVFs). PATIENTS AND METHODS: Retrospective review of medical records of all patients with the diagnosis of PAVF evaluated at Mayo Clinic Rochester from 1982 through 1997. Demographic characteristics, presence or absence of hereditary hemorrhagic telangiectasia, clinical features, and results of imaging studies and blood gas analyses, treatments, and complications related to PAVFs were reviewed. RESULTS: Among the 93 patients, 44 were male and 49 female. The mean age at the time of evaluation was 40 years (range, 5-83 years). Fifteen patients (16%) were asymptomatic. History of hereditary hemorrhagic telangiectasia was present in 52 patients (56%). Notable clinical findings included epistaxis in 46 (49%), hemoptysis in 14 (15%), cyanosis in 27 (29%), clubbing in 18 (19%), dyspnea in 53 (57%), and pulmonary bruits/murmurs in 32 (34%). Chest x-ray films with or without tomograms showed abnormal findings in 87 (94%), of which 68 (73%) suggested PAVF. Polycythemia was detected in 12 (13%). Pretherapy arterial PO2 measured on room air averaged 56 mm Hg (range, 32-95 mm Hg), and the posttherapy PO2 averaged 77 mm Hg (range, 46-110 mm Hg). Echocardiography with indocyanine green dye was diagnostic of extracardiac right-to-left shunt in 26 (90%) of 29 patients tested. Diagnostic studies revealed single lesions in 32 patients (34%) and multiple lesions in 61 (66%). The most prominent complications of the disease were neurologic events in 34 patients (37%). These complications included transient ischemic attacks, hemiplegia, brain abscesses, and seizures. Surgical resection alone was carried out in 18 patients (19%), embolization therapy alone in 41 (44%), and both therapies in 7 (8%). The 48 patients treated with embolization required 78 embolization sessions with more than 200 lesions occluded. Complications of treatment included postembolization hemothorax in 1 patient and right-sided hemiparesis in another patient. Follow-up disclosed that 1 patient died from PAVF-related complications. CONCLUSIONS: Among our patients with PAVFs, hereditary hemorrhagic telangiectasia was observed in more than half and neurologic complications in more than one third. Because of the considerable risk of neurologic and other complications, definitive treatment should be considered in patients with PAVFs. Embolization is currently the preferred treatment in most patients. Frequent follow-up of treated patients is necessary because PAVFs tend to increase both in number and in size over time.

Radiation-induced pneumonitis in the "nonirradiated" lung.

OBJECTIVE: To describe six cases of radiation-induced organizing pneumonitis occurring outside the direct radiation field and to review clinical, radiologic, and histologic aspects of this entity. MATERIAL AND METHODS: We present detailed case reports of six women, with a mean age of 62.8 years (range, 50 to 75), who had received radiation therapy (mean dose, 6,560 cGy) for breast cancer. RESULTS: From 6 to 17 months (mean, 8.8) after the completion of radiotherapy, recurrent and migrating lung infiltrates were detected outside the radiation field in the six study patients. Three patients had pronounced respiratory symptoms, whereas the rest were minimally symptomatic or asymptomatic. Thoracic computed tomography showed dense alveolar infiltrates. Bronchoalveolar lavage in two patients revealed lymphocytosis (25% and 19%), and lung biopsy in five patients demonstrated a histologic pattern consistent with bronchiolitis obliterans organizing pneumonia. Even though the symptomatic patients showed prompt resolution of their symptoms and roentgenographic abnormalities after systemic corticosteroid therapy, the lung infiltrates recurred after corticosteroid therapy was discontinued. CONCLUSION: These six cases, including their prompt response to corticosteroid therapy, provide additional evidence that irradiation damages lung tissue outside of the direct treatment field and suggest that an immunologically mediated lymphocytic alveolitis may be responsible for the recurrent migratory organizing pneumonitis.

Rapidly growing mycobacterial lung infection in association with esophageal disorders.

Esophageal or other swallowing disorders complicated by lipoid pneumonia are reported to be associated with pulmonary infections caused by rapidly growing mycobacteria. Herein we describe a 63-year-old woman with achalasia of the esophagus complicated by lung infection with Mycobacterium chelonae and a 47-year-old man in whom long-term ingestion of mineral oil was complicated by lipoid pneumonia and M. fortuitum lung infection. A MEDLINE search of English language publications from 1966 to 1997 revealed 18 cases of lung infections caused by rapidly growing mycobacteria in patients with esophageal disorders. Of these 18 patients and our 2 patients, 11 were men and 9 were women (mean age, 50 years). Achalasia was present in 11 patients, and 6 had lipoid pneumonia without evidence of esophageal disorders. Three patients had lipoid pneumonia caused by lipoid ingestion in the setting of achalasia or another swallowing disorder. In 14 patients, lung infection was caused by M. fortuitum; in 5, M. chelonae; and in 1, a non-M. fortuitum rapidly growing mycobacterial infection. The most common clinical feature was fever, and the most common roentgenologic abnormality was the presence of unilateral or bilateral and patchy or dense infiltrates. The sputum was the most common source of isolation of rapidly growing mycobacteria. Achalasia and lipoid pneumonia are important risk factors for the development of lung infections caused by rapidly growing mycobacteria. Treatment of the esophageal disease might prevent occurrence of and facilitate recovery from these infections.

Chest roentgenography after outpatient thoracentesis.

OBJECTIVE: To evaluate the clinical utility of posteroanterior chest roentgenograms after thoracentesis in the outpatient setting. DESIGN: We undertook a retrospective study of clinical records of outpatient thoracentesis performed between January and December 1996 by the Division of Pulmonary and Critical Care Medicine at Mayo Clinical Rochester. MATERIAL AND METHODS: The medical records of 54 men and 39 women who underwent 123 outpatient thoracentesis were reviewed. Exclusion criteria were the need for pleural biopsy at time of thoracentesis or the need for ultrasound-guided assistance for completion of the procedure. Indications for thoracentesis and postthoracentesis chest roentgenography were analyzed. RESULTS: Of 123 thoracentesis performed in the outpatient setting during the specified study period, 104 met the inclusion criteria. Of these 104 thoracentesis, 54 (52%) were followed by chest roentgenography. Pneumothorax occurred in only 5 of these 104 procedures (5%), in 5 separate patients. Three of these patients were asymptomatic and did not require therapeutic intervention; the two symptomatic patients required hospitalization and chest tube drainage. Of the two pneumothoraces in patients with symptoms, one was detected on the same day as the thoracentesis, and the other was diagnosed 2 days later. The patients who did not undergo postthoracentesis chest roentgenography had no reported complications. Of the 54 chest roentgenograms, 52 were obtained in asymptomatic patients, with no suspicion of pneumothorax. These x-ray studies led to a total cost of $4,862 and detection of three pneumothoraces that did not require therapy. CONCLUSION: Routine performance of chest roentgenography after outpatient thoracentesis can incur substantial cost. A more selective approach to this practice is needed, both to optimize patient care and to manage limited medical resources efficiently. Postthoracentesis chest roentgenograms should be limited to patients with symptoms indicative of thoracentesis-induced pneumothorax.

Respiratory complications in mixed connective tissue disease.

The term mixed connective tissue disease is used to identify the patients with combined clinical features of systemic lupus erythematosus, scleroderma or progressive systemic sclerosis, and polymyositis-dermatomyositis. A prerequisite for the diagnosis of mixed connective tissue disease is the presence, in the serum, of high titers of antibodies against uridine-rich RNA-small nuclear ribonucleoprotein (snRNP). Respiratory and nonrespiratory features of the disease follow those seen in systemic lupus erythematosus, scleroderma, or progressive systemic sclerosis, and polymyositis-dermatomyositis. Respiratory involvement is observed in 20% to 80% of patients. Major respiratory manifestations and their incidences described include interstitial pneumonitis and fibrosis (20% to 65%), pleural effusion (50%), pleurisy (20%), and pulmonary hypertension (10% to 45%). Other pulmonary features consist of pulmonary vasculitis, pulmonary thromboembolism, aspiration pneumonia, pulmonary hemorrhage, pulmonary nodules, pulmonary cysts, obstructive airways disease, mediastinal lymphadenopathy, pulmonary infections, hypoventilatory respiratory failure, and diaphragmatic dysfunction. Pulmonary hypertension is a serious complication; rapid deterioration and death have occurred in spite of corticosteroid and cytotoxic chemotherapy.

alpha1-antitrypsin gene mutation hot spot associated with the formation of a retained and degraded null variant [corrected; erratum to be published].

Null alpha1-antitrypsin (alpha1AT) alleles represent the end of a continuum of variants associated with profound alpha1AT deficiency and an increased risk of emphysema. This study characterizes the molecular basis of QOclayton, a new example of an alpha1AT null allele arising from a mutational hot spot in the alpha1AT gene. The QOclayton allele is identical to the normal M1(V213) alpha1AT allele except for an insertion of a cytosine. This insertion occurs in the alpha1AT sequence which normally has seven cytosines corresponding to amino acid residues 360 to 362. The QOclayton mutation is located in the same reiterated DNA sequence as the alpha1AT QObolton deletion mutation and the insertion mutation allele QOsaarbruecken. The QOclayton cytosine insertion causes a 3' frameshift and results in the formation of a termination codon at residue 376, the same consequence as the alpha1AT QOmattawa mutation (L353 T-insertion with a 3' frameshift). To determine the molecular mechanisms responsible for the absence of alpha1AT associated with the QOclayton gene, an in vitro model of QOclayton was established using Chinese hamster ovary cells (CHO) transfected with the QOclayton gene. These cells were evaluated for alpha1AT mRNA expression, protein synthesis and secretion. Although the QOclayton gene expresses a similar amount of alpha1AT mRNA as compared with the normal alpha1AT gene, no QOclayton protein is secreted. Protein trafficking and double-label immunofluorescence demonstrate that the QOclayton protein is retained in the rough endoplasmic reticulum or pre-Golgi compartment and is degraded (t1/2 = 6.5 h). Since QOmattawa, QObolton, and QOsaarbruecken have similar termination sites in the alpha1AT mRNA, they may share a similar intracellular fate.