Nasal and pharyngeal eosinophil peroxidase levels in adults with poorly controlled asthma correlate with sputum eosinophilia.

The objective of the study was to compare nasal, pharyngeal, and sputum eosinophil peroxidase (EPX) levels with induced sputum eosinophil percentage in 10 adults with poorly controlled asthma and 10 normal controls. EPX was measured using an ELISA and normalized for grams of protein for nasal and pharynx specimens and for mL-gram of protein for sputum. Sputum EPX levels were statistically different between asthma and control subjects (P = 0.024). EPX levels measured in the nasal and pharyngeal swab samples derived from the same patients were also different between asthma and control subjects, each displaying a high degree of significance (P = 0.002). Spearman's correlation coefficients for nasal EPX and pharyngeal EPX levels compared to induced sputum eosinophil percentage were 0.81 (P = 0.0007) and 0.78 (P = 0.0017), respectively. Thus, there is a strong association in a given patient between both nasal and pharyngeal EPX levels and the eosinophil percentage of induced sputum.

Surgical pathology of granulomatous interstitial pneumonia.

Agranulomatous interstitial pneumonia is a form of diffuse lung disease in which granulomas are a component of the histologic findings. The differential diagnosis is quite broad, but most cases represent examples of either sarcoidosis, diffuse granulomatous infections, or hypersensitivity pneumonitis. "Hot tub lung" is a recently described form of granulomatous interstitial pneumonia that appears to have some features of diffuse infections and some features of hypersensitivity pneumonitis. The pathologist's approach to these conditions can be facilitated by giving careful attention to the anatomic distribution of the granulomas, the qualitative features of the granulomas, and the histologic changes in the lung tissue around and away from the granulomas. These features, along with the results of cultures and special stains for micro-organisms and clinical and radiologic correlation allow for a diagnosis in the vast majority of cases.

Diffuse pulmonary disease caused by nontuberculous mycobacteria in immunocompetent people (hot tub lung).

The clinicopathologic spectrum of infections due to nontuberculous mycobacteria (NTM) includes cavitary disease, opportunistic infection, and nodular disease associated with bronchiectasis. We report a less well-described manifestation of NTM infection: 10 immunocompetent patients without preexisting bronchiectasis had radiographic evidence of diffuse infiltrative lung disease. The most common symptoms were dyspnea, cough, hypoxia, and fever. All 10 patients had used a hot tub. Histologic examination revealed exuberant nonnecrotizing, frequently bronchiolocentric, granulomatous inflammation in all cases. In 1 case, necrotizing granulomas were also noted. The inflammation often was associated with patchy chronic interstitial pneumonia and organization. Cultures revealed NTM in all cases (Mycobacterium avium complex in all but 1 case), but staining for acid-fast bacilli was positive in only 1 case. Four patients received corticosteroids alone for presumed hypersensitivity pneumonia, 4 were treated with antimycobacterial therapy, and 2 received both. All patients demonstrated significant improvement at the time of follow-up. These findings suggest that disease due to NTM may manifest as diffuse infiltrates in immunocompetent adults and that hot tub use may be an important risk factor for this disease pattern.

Methotrexate pneumonitis: review of the literature and histopathological findings in nine patients.

Pneumonitis is a serious and unpredictable side-effect of treatment with methotrexate (MTX) that may become life-threatening. The clinical and histological features of nine cases of MTX pneumonitis are reported and the literature reviewed. The typical clinical symptoms include progressive shortness of breath and cough, often associated with fever. Hypoxaemia and tachypnoea are always present and crackles are frequently audible. Chest radiography reveals a diffuse interstitial or mixed interstitial and alveolar infiltrate, with a predilection for the lower lung fields. Pulmonary function tests show a restrictive pattern with diminished diffusion capacity. Lung biopsy reveals cellular interstitial infiltrates, granulomas or a diffuse alveolar damage pattern accompanied by perivascular inflammation. These clinical and pathological findings are not specific to MTX pneumonitis and can be seen with other drug-induced lung toxicities. It is important that all patients receiving methotrexate be educated concerning this potential adverse reaction and instructed to contact their physicians should significant new pulmonary symptoms develop while undergoing therapy. If methotrexate pneumonitis is suspected, methotrexate should be discontinued, supportive measures instituted and careful examination for different causes of respiratory distress conducted.

Pulmonary infiltrates, eosinophilia, and cardiomyopathy following corticosteroid withdrawal in patients with asthma receiving zafirlukast.

CONTEXT: Zafirlukast is a potent leukotriene antagonist that recently was approved for the treatment of asthma. As use of this drug increases, adverse events that occur at low frequency or in populations not studied in premarketing clinical trials may become evident. OBJECTIVE: To describe a clinical syndrome associated with zafirlukast therapy. DESIGN: Case series. PATIENTS: Eight adults (7 women and 1 man) with steroid-dependent asthma who received zafirlukast. MAIN OUTCOME MEASURES: Development of a clinical syndrome characterized by pulmonary infiltrates, cardiomyopathy, and eosinophilia following the withdrawal of corticosteroid treatment. RESULTS: The clinical syndrome developed while patients were receiving zafirlukast from 3 days to 4 months and from 3 days to 3 months after corticosteroid withdrawal. All 8 patients developed leukocytosis (range, 14.5-27.6 x 10(9)/L) with eosinophilia (range, 0.19-0.71). Six patients had fever (temperature >38.5 degrees C), 7 had muscle pain, 6 had sinusitis, and 6 had biopsy evidence of eosinophilic tissue infiltration. The clinical syndrome improved with discontinuation of zafirlukast treatment and reinitiation of corticosteroid treatment or addition of cyclophosphamide treatment. COMMENT: Development of pulmonary infiltrates, cardiomyopathy, and eosinophilia may have occurred independent of zafirlukast use or may have resulted from an allergic response to this medication. We suspect that these patients may have had a primary eosinophilic infiltrative disorder that had been clinically recognized as asthma, was quelled by steroid treatment, and was unmasked following corticosteroid withdrawal facilitated by zafirlukast.

Rigid bronchoscopy. The forgotten art.

Rigid bronchoscopy is superior to flexible fiberoptic bronchoscopy in several clinical situations. General anesthesia is usually used with side port ventilation. In children, removal of foreign bodies is an important indication. Tracheal stricture dilatation and cryotherapy are indications in adults, but laser bronchoscopy has become the major indication for rigid bronchoscopy in adult medicine.

Recurrent bronchogenic pseudocyst 24 years after incomplete excision. Report of a case.

Bronchogenic cysts (BCs) are uncommon congenital anomalies. Due to the inherent complications, the mere presence of a BC should warrant surgical therapy. Partial excision of these structures leads to recurrence. Complete surgical excision using a thoracotomy or video-assisted thoracic surgery is the goal. We report a case of recurrent bronchogenic pseudocyst 24 years after initial excision. This case supports the argument for complete surgical excision of BCs at the time of diagnosis.

Determinants of progression in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive form of lung disease with a median survival of less than 5 yr. To address the progressive nature of this disease process, we investigated the determinants of decrements in lung function in patients with IPF. We prospectively evaluated 39 subjects with IPF. Our study subjects were followed for an average of 2 yr (range, 49 to 1,883 days) and lung function was measured on at least two separate occasions (mean = 9.1 separate tests) during the follow-up period. Since IPF is characterized by reduced lung volume and abnormal gas exchange, our analysis focused on the determinants of total lung capacity (TLC) and diffusing capacity of carbon monoxide (DLCO) during the period of observation. Although, on average, there was a 5.3% increase in the TLC and a 9.8% increase in DLCO between the first and last measure of lung function, 25% of the study population experienced a decline in the TLC and 28% of the study population experienced a decline in the DLCO. Decrements in TLC were independently associated with severe dyspnea (p = 0.01) and treatment with cyclophosphamide (p = 0.03). Decrements in DLCO were significantly and independently associated with more pack-years of cigarette smoking (p = 0.02), moderate (p = 0.03) or severe (p = 0.02) dyspnea, and treatment with cyclophosphamide (p = 0.0002). These findings indicate that several clinical characteristics are independently associated with subsequent declines in TLC and DLCO in patients with IPF.(ABSTRACT TRUNCATED AT 250 WORDS)

Determinants of survival in idiopathic pulmonary fibrosis.

To identify the determinants of survival in patients with idiopathic pulmonary fibrosis (IPF), we performed a survival analysis on 74 subjects with IPF. The study subjects were on average 64 yr of age (range, 25 to 83 yr), 62% were male, and 29% were never smokers. A tissue diagnosis was made in 67 (91%) of our study subjects. These subjects were followed for a mean period of 4 yr (range, 1.4 to 118.8 months) after the onset of pulmonary symptoms. During the period of observation, 41 subjects died (median survival = 28.2 months) and 33 continue to survive (median follow-up period = 60.9 months). A univariate analysis demonstrated that diminished survival was significantly associated with male gender (hazard ratio = 1.98; 95% confidence interval [CI] = 1.01-3.85), a higher FEV1/FVC ratio (hazard ratio = 1.82 [per 10% increase in the FEV1/FVC ratio]; 95% CI = 1.21-2.73), a lower percent predicted FVC (hazard ratio = 0.74; 95% CI = 0.60-0.91), a lower percent predicted total lung capacity (TLC) (hazard ratio = 0.75; 95% CI = 0.60-0.94), a lower percent predicted diffusing capacity of carbon monoxide (DLCO) (hazard ratio = 0.69; 95% CI = 0.53-0.89), a higher ILO profusion category on chest radiograph (hazard ratio = 3.52; 95% CI = 1.58-7.87), and an enhanced release of prostaglandin E2 (PGE2) by cultured alveolar macrophages (hazard ratio = 1.32 [per 10 pm/ml of PGE2]; 95% CI = 1.07-1.62).(ABSTRACT TRUNCATED AT 250 WORDS)

Outcome of subjects with idiopathic pulmonary fibrosis who fail corticosteroid therapy. Implications for further studies.

To evaluate the outcome of subjects with idiopathic pulmonary fibrosis (IPF) whose conditions clinically deteriorate while receiving corticosteroid therapy, we studied 12 of these subjects (7 male, 5 female) who received subsequent therapy with intravenous (IV) pulse cyclophosphamide (CPX). Seven of the 12 study subjects died during the course of therapy. Six of these subjects died of respiratory failure, and one died of cholecystitis. Among those who died, the mean age at diagnosis was 63 years compared with 57 years in those who have continued to survive (p = 0.29). Smoking status and pack-years of cigarette smoking were similar between those subjects who died and those who continue to survive. However, subjects who died received CPX for a mean of 6 months, while subjects still living have received CPX for a mean of 16 months (p = 0.01). Subjects who died were given a CPX a mean of 64 months after the onset of symptoms, compared with a mean of 50 months for subjects who are still alive (p = 0.57). Interestingly, there were no significant differences in measures of pulmonary function between living and dead subjects. In fact, measures of lung function and gas exchange remained stable in both groups throughout the period of observation. These data suggest that (1) measures of lung function may not be a reliable indicator of patient mortality in end-stage IPF, and (2) while not statistically significant, these data raise the possibility that duration of symptomatic disease may play a role in the outcome of IPF patients receiving alternative therapeutic agents after failure of corticosteroid therapy. In future intervention trails, controlling entry criteria for duration of disease may prove helpful in determining the effects of these agents on the disease process. These data do not permit a determination of the effect of CPX in patients with IPF.

Bronchoalveolar lavage cellularity. The distribution in normal volunteers.

Bronchoalveolar lavage (BAL) is used to obtain inflammatory cells from the lung. For clinical research, parametric statistics are frequently used to compare cells present in BAL of patients with lung disease with cells present in BAL of normal subjects. To determine if these populations can be compared in this manner we performed BAL on 111 never-smoking, normal volunteers and determined: (1) the mean, median, standard deviation, and range of the cells in BAL; (2) whether the data are normally distributed and satisfy the criteria for use of parametric statistical analysis. The BAL cellularity was expressed as a percentage of total cells, cells per milliliter return, and total cells per lavage. Regardless of the means of expression, no measure of BAL cellularity (total cells, macrophages, lymphocytes, neutrophils, or eosinophils) conformed to the normal (bell-shaped) distribution when tested for goodness of fit with the G statistic (all p < 0.001). The lack of fit to the normal distribution was not substantially altered by either the method of expressing the data (i.e., cells per milliliter, total cells, or percent of cells) or log transformation of the data. The poor fit in all cases resulted from clumping of the data about the mean and large tails. The percent of cells were, therefore, tested for goodness of fit to the Poisson distribution, a distribution of discrete variables. The neutrophil and eosinophil percentages resulted in an excellent fit to the Poisson distribution, but macrophage and lymphocyte percentages did not.(ABSTRACT TRUNCATED AT 250 WORDS)

Determinants of bronchoalveolar lavage cellularity in idiopathic pulmonary fibrosis.

To investigate factors that determine bronchoalveolar lavage (BAL) cellularity in patients with idiopathic pulmonary fibrosis (IPF), we compared BAL cells in patients with IPF (n = 83) to both nonsmoking (n = 111) and smoking (n = 19) normal volunteers. Patients with IPF had higher concentrations of BAL total cells and alveolar macrophages than nonsmoking volunteers and more BAL neutrophils and eosinophils than normal volunteers regardless of smoking status. Among patients with IPF, the numbers of alveolar macrophages, neutrophils, or eosinophils were strongly associated with either smoking status or pack-years of cigarette smoking. In fact, after accounting for cigarette smoking, using multivariate analysis, the only additional factors that were found to be associated with BAL cellularity were age (macrophages and eosinophils) and the percent predicted forced expired volume in 1 s (neutrophils). Additional multivariate models failed to identify a significant relationship between BAL cellularity and either the type of immunosuppressive therapy or other physiological measures of lung function. We conclude that cigarette smoking strongly influences BAL cellularity in patients with IPF. These findings suggest that cigarette smoking may have a role in the pathogenesis of IPF or may adversely affect the prognosis in patients with IPF.

The influence of cigarette smoking on lung function in patients with idiopathic pulmonary fibrosis.

The purpose of this investigation was to quantify the effect of cigarette smoking on standard measures of lung function in patients with idiopathic pulmonary fibrosis (IPF). Our study population consisted of 73 patients in whom IPF had been clinically diagnosed; in 67% the diagnosis was confirmed by open lung biopsy. The average age was 63 yr; 62% were men, and 70% were either former or current cigarette smokers. Current cigarette smokers were found to have a greater percent predicted residual volume. Interestingly, in a univariate analysis, pack-years of cigarette smoking was found to be directly associated with increased measures of lung volumes (TLC, FRC, and RV) and diminished gas exchange (DLCO). Linear multivariate regression models demonstrated that current cigarette smokers have greater measures of RV and FRC and that increasing pack-years of cigarette smoking is associated with diminished gas exchange. Importantly, the FEV/FVC ratio was not significantly related to either smoking status or pack-years of cigarette smoking. Results from our study indicated that among patients with IPF, current cigarette smokers will tend to trap air (higher RV and FRC), and that cigarette smoking appears to adversely alter gas exchange. Moreover, IPF appears to reduce the likelihood of developing physiologic correlates of airflow obstruction among cigarette smokers. However, this does not imply that IPF prevents the development of cigarette-induced lung disease. In fact, the association between cigarette smoking and both increased lung volumes and diminished gas exchange suggests the presence of both emphysema and interstitial fibrosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Sarcoidosis and giant splenomegaly.

Splenomegaly is often a manifestation of sarcoidosis, but giant splenomegaly is rare. Only 25 cases of sarcoidosis presenting as massive splenomegaly have been reported. Splenectomy was performed before the diagnosis of sarcoidosis was made in more than half of these patients. Serious complications of giant splenomegaly including rupture, severe thrombocytopenia and hemolytic anemia were not consistently present preoperatively. A case of disseminated sarcoidosis presenting with giant splenomegaly and normal chest roentgenograms is described. Prednisone therapy improved the patient's pulmonary function testing while constitutional symptoms, splenomegaly and elevated angiotensin-converting enzyme levels completely resolved. Sarcoidosis should be considered in the differential diagnosis of massive splenomegaly. A trial of steroids is warranted as initial treatment, and in selected cases may prevent unnecessary splenectomy, thereby precluding a compromise in host defenses against encapsulated bacteria.

Bronchoalveolar lavage in interstitial lung disease: effect of volume of fluid infused.

To evaluate the effect of varying infusate volume on the results of bronchoalveolar lavage (BAL) in patients with interstitial lung disease, 55 patients underwent 58 BAL during which both a 100- and 250-ml lavage was performed in the same lobe of the lung. Although the percent of the fluid that was returned and the total numbers of cells were greater in the 250- vs. the 100-ml lavage, there were no significant differences in cell differentials or numbers of cells per milliliter between the 100- and 250-ml BAL. We conclude that infusate volume does not affect cell differentials or numbers of cells per milliliter of bronchoalveolar lavage fluid in patients with interstitial lung disease.

Serial exercise testing in pulmonary embolism.

A patient underwent exercise testing during evaluation for unexplained dyspnea. Evidence of ventilation-perfusion mismatch was noted and subsequent testing revealed multiple pulmonary emboli. Ventilation perfusion parameters by serial exercise testing progressively improved during the course of the patient's illness but did not totally normalize. A discussion of the utility of exercise testing in the evaluation of the patient with unexplained dyspnea is provided and the potential value of serial exercise testing in the management of patients with pulmonary emboli is discussed.