Cavitary Disease Research Articles

Detailed Analysis of the Radiographic Presentation of Mycobacterium kansasii Lung Disease in Patients With HIV Infection

Published criteria for the diagnosis of Mycobacterium kansasii lung disease require the presence of clinical symptoms, positive microbiologic results, and radiographic abnormalities. In patients with HIV infection, the radiographic findings of M kansasii lung disease are not well described. Medical records and chest radiographs of all patients with HIV infection and at least one respiratory specimen culture positive for M kansasii at San Francisco General Hospital between December 1989 and July 2002 were reviewed. Chest radiographic results were abnormal in 75 of 83 patients (90%) included in the study. Radiographic abnormalities were diverse, with consolidation (66%) and nodules (42%) as the most frequent findings. The mid or lower lung zones were involved in 89% of patients. The pattern of radiographic abnormalities did not differ based on acid-fast bacilli smear status, the presence or absence of coexisting pulmonary infections, or CD4+ T-lymphocyte count. In multivariate Cox regression analysis, cavitation was the only radiographic abnormality independently associated with mortality (hazard ratio, 4.8; 95% confidence interval, 1.2 to 19.6). Patients with HIV infection and M kansasii lung disease present with diverse radiographic patterns, most commonly consolidation and nodules predominantly located in the mid and lower lung zones. This finding is in contrast to the upper-lobe cavitary presentation described in patients without HIV infection. Although rare, the presence of cavitary disease in patients with HIV infection and M kansasii independently predicts worse outcome. The diversity in the radiographic presentation of M kansasii lung disease implies that clinicians should obtain sputum mycobacterial culture samples from any patient with HIV infection and an abnormal chest radiograph finding.

Diagnostic Accuracy of Cytokine Levels (TNF-α, IL-2 and IFN-γ) in Bronchoalveolar Lavage Fluid of Smear-Negative Pulmonary Tuberculosis Patients

Background: The determination of cytokine concentrations in serum and bronchoalveolar lavage fluid (BALF) may contribute to the diagnosis of tuberculosis (TB) since cytokines have been ascribed an important role in TB pathogenesis. Objective: To assess the diagnostic accuracy of TNF-α, IFN-γ and IL-2 levels in serum and BALF of smear-negative pulmonary TB patients. Method: BALF was obtained from the affected lobe in patients with smear-negative TB or other pulmonary diseases (OPD), and from the right middle lobe in healthy controls. ELISA and a nephelometric method were used to detect cytokine and albumin levels. Results: TNF-α levels in BALF were significantly elevated in the TB group (n = 15) compared with the OPD patients (n = 40) and controls (n = 17; p < 0.001). Although these three cytokines correlated well with each other in BALF (p < 0.0001, and r ≧ 0.7, respectively), BALF IL-2 and IFN-γ levels were not significantly different among the groups (p > 0.05). BALF TNF-α or IFN-γ levels were significantly higher in patients with cavitary disease (n = 11) versus those without (n = 61; p < 0.05). However, no significant difference was found between cavitary (n = 7) and non-cavitary TB in cytokine levels (p > 0.05). Neither gender nor smoking status showed any statistical differences in cytokines in the groups (p > 0.05). Sensitivity and specificity of BALF TNF-α were found to be 73 and 76%, respectively. The positive and negative predictive values for BALF TNF-α were 44 and 91%, respectively. Conclusion: In cases of smear-negative TB, BALF TNF-α can be a useful tool to identify healthy subjects rather than smear-negative TB patients.

Cavitary Disease and Quantitative Sputum Bacillary Load in Cases of Pulmonary Tuberculosis

We examined sputum bacterial loads in adults with newly diagnosed tuberculosis using quantitative culture and time-until-positive (DTP) culture in BACTEC 460. Patients with cavitary disease had higher CFU levels than those without cavities and shorter DTPs. Within radiographic strata of moderately and far advanced tuberculosis, higher CFU counts were associated with cavitary disease.

Hemorrhagic pulmonary oxalosis secondary to a noninvasive Aspergillus niger fungus ball

We report a case of hemorrhagic pulmonary oxalosis secondary to a noninvasive Aspergillus niger fungus ball. A patient with cavitary lung disease and hemoptysis developed progressive lung infiltrates and intractable metabolic acidosis leading to death. At autopsy, aspergillomas were identified in both the right upper and middle lobes surrounded by a large rim of necrotic and hemorrhagic parenchyma. Microscopic examination showed extensive crystal deposition and vascular thrombosis. Fungal growth was limited to the intraluminal mycelia, and no tissue or blood vessel invasion was present. Remote crystal deposits were also localized in the absence of fungal organisms to the contralateral lung and to the tubules of both kidneys. The crystals were birefringent in polarized light and stained with colloidal iron. X-ray powder diffractometry and electron impact ionization mass spectrometry identified the crystals as calcium oxalate monohydrate. Furthermore, non-necrotizing granulomatous lesions were identified in the lungs, liver, and spleen, consistent with sarcoidosis, and may have predisposed this patient to developing pulmonary aspergillomas.

Aspiration pneumonia and primary lung abscess: diagnosis and therapy of an aerobic or an anaerobic infection?

Pneumonia and primary lung abscesses may result from aspiration of infectious material from the oropharyngeal cavity and the upper respiratory tract. Most subjects suffer from an impaired mechanical or immunologic defense, for example alcoholism or dysphagia following stroke. The early course of the disease is uncharacteristic. Necrotizing pneumonia, pulmonary abscesses and the characteristic, foul-smelling, putrid discharge only occur 8–14 days after the initial aspiration event. Although common respiratory pathogens are frequently isolated from the lower airways of these patients, anaerobic bacteria play a pivotal role in cavitary lung disease following aspiration. Anaerobic coverage is therefore a requirement for an adequate antibiotic regimen, and antibacterial activity against common respiratory pathogens appears reasonable in most cases. Aminopenicillins/β-lactamase inhibitors, newer fluoroquinolones with anaerobic activity (moxifloxacin) and clindamycin have demonstrated equal clinical efficacy in the treatment of aspiration pneumonia and primary lung abscess. Prolonged antibiotic therapy is required in cases with extensive damage of lung tissue. Since antibiotics can provide cure in 80–90% of cases, surgical procedures are limited to severe complications, such as pleural empyema. Cavitary lung disease has a broad differential diagnosis, including aspiration of sterile gastric content (Mendelson syndrome), staphylococcal pneumonia, tuberculosis, primary carcinoma of the lung, metastases and vasculitis.

LEGIONELLA BOZEMANII PULMONARY ABSCESS IN A PEDIATRIC ALLOGENEIC STEM CELL TRANSPLANT RECIPIENT

Legionella spp. infections are often considered in the differential diagnosis of pneumonia in adults. This case report describes a pediatric stem cell transplant recipient presenting with cavitary pulmonary disease secondary to Legionella bozemanii infection. Also highlighted with this atypical clinical presentation are challenges in diagnosing legionellosis and concerns of increased vulnerability for such infections when severely immunocompromised patients are changed to nontrimethoprim-sulfamethoxazole Pneumocystis jiroveci pneumonia prophylaxis.

Redefining the Clinical Spectrum of Chronic Pulmonary Histoplasmosis

Chronic pulmonary histoplasmosis is a disorder caused by Histoplasma capsulatum infection that is classically described as cavitary disease in male smokers with underlying chronic obstructive pulmonary disease (COPD). This clinical description relies on previous studies conducted mainly on cohorts from tuberculosis sanatoriums and United States Department of Veterans Affairs hospitals. Patients in earlier series were often selected either after being suspected of having Mycobacteria tuberculosis or by the presence of cavitary disease on chest radiograph. These early studies therefore may overrepresent the true proportion of males, smokers, and the percentage with cavitary disease in the general population. We sought to define the clinical spectrum of chronic pulmonary histoplasmosis in a mixed-sex inpatient and outpatient population. We conducted a retrospective chart review from 1976 to 2000 on all adults with a diagnosis of histoplasmosis with symptoms suggestive of pulmonary histoplasmosis for > or =6 weeks and either significantly positive serum H. capsulatum antibody titers or positive cultures (without evidence of disseminated disease). Participants included 46 patients, with a median age of 56 years. Notable differences were found between our study population and those in previously reported studies. First, nearly half of our patients were women (48%), and one-quarter were life-long nonsmokers (27%). Only 39% had cavitary disease and only 20% had COPD. It is noteworthy that there were no positive cultures from those patients who had never smoked. Major differences existed between male and female participants. Female patients had a lower presence of cavities, a decreased number of smokers and extent of smoking exposure, a decreased number of positive cultures, and an absence of underlying COPD. To our knowledge, this study is the first to report on a large number of outpatients with chronic pulmonary histoplasmosis. In contrast to previous studies, the current study included 48% female patients, 27% never smokers, and only 39% of patients with cavitary disease, representing a noticeably different spectrum of disease compared to previous studies.

The Many Faces of Pulmonary Nontuberculous Mycobacterial Infection

The purpose of this article is to review clinical and radiologic manifestations of pulmonary nontuberculous mycobacterial infection. Common and well-recognized patterns of infection include cavitary and bronchiectatic disease and infection in AIDS patients. Less common or well-recognized manifestations include nodules or masses mimicking malignancy, hypersensitivity pneumonitis, and others. Definitive diagnosis can be difficult and patterns may overlap. Timely diagnosis requires a high index of suspicion and knowledge of the spectrum of clinical and radiologic features.

Clinical manifestations of tuberculosis in children

The natural history and clinical manifestations of tuberculosis in children differ significantly from those of the disease seen in adults. The two main factors determining the risk of progression to disease are patient age and immune status. Neonates have the highest risk of progression to disease, and in infancy miliary and meningeal involvement is common. Children from 5 to 10 years of age are less likely to develop disease than other age groups, and adolescent patients can present with progressive primary tuberculosis or cavitary disease. Immunocompromised patients are more likely both to progress to tuberculous disease and to have extrapulmonary manifestations; diagnostic tests are also of lower yield in this population. The most common sites of disease in children are intrathoracic disease and superficial lymphadenopathy. Clinical manifestations are often due to a profound inflammatory response to a relatively low burden of organisms. This is reflected in the low yield of diagnostic tests; consequently, the diagnosis of tuberculosis is often based upon a positive skin test, epidemiological information, and compatible clinical and radiographic presentation.

Pulmonary aspergillosis: a clinical update

Aspergillus spp may cause a variety of pulmonary diseases, depending on immune status and the presence of underlying lung disease. These manifestations range from invasive pulmonary aspergillosis in severely immunocompromised patients, to chronic necrotizing aspergillosis in patients with chronic lung disease and/or mildly compromised immune systems. Aspergilloma is mainly seen in patients with cavitary lung disease, while allergic bronchopulmonary aspergillosis is described in patients with hypersensitivity to Aspergillus antigens. Recent major advances in the diagnosis and management of pulmonary aspergillosis include the introduction of non-invasive tests, and the development of new antifungal agents, such as azoles and echinocandins, that significantly affect the management and outcome of patients with pulmonary aspergillosis. This review provides a clinical update on the epidemiology, risk factors, clinical presentation, diagnosis and management of the major syndromes associated with pulmonary aspergillosis.

Metastatic Adenocarcinoma of the Breast Presenting as Cavitary Lung Disease

Metastatic Adenocarcinoma of the Breast Presenting as Cavitary Lung Disease

Bronchoalveolar neutrophils, interferon gamma-inducible protein 10 and interleukin-7 in AIDS-associated tuberculosis

During advanced AIDS tuberculosis (TB) often presents atypically with smear-negative and non-cavitary disease, yet immune features associated with this change are poorly characterized. We examined the local immune response in a cohort of Tanzanian AIDS-associated TB patients who underwent bronchoalveolar lavage. TB infection was confirmed in bronchoalveolar lavage (BAL) fluid by culture, probe and polymerase chain reaction (PCR). Among TB patients CD4 count correlated positively with the extent of cavitary disease as well as BAL TB load (qPCR CT). TB patients had significantly higher granulocyte–macrophage colony-stimulating factor (GM-CSF) than non-TB patients, and those with non-cavitary TB had significantly higher BAL interferon gamma-inducible protein (IP-10) and interleukin (IL)-7 than those with cavities. BAL neutrophils were as prevalent as monocytes/macrophages or epithelial cells, and immunohistochemistry revealed that neutrophils, monocytes/macrophages, and epithelial cells were major sources of the IP-10 and IL-7. These data suggest a dysregulated cytokine profile may contribute to the TB of advanced AIDS.

Mycobacterium Avium Complex Infection Presenting as an Endobronchial Mass in a Patient with Acquired Immune Deficiency Syndrome

Mycobacterium avium complex (MAC) infection is a common opportunistic infection in patients with AIDS (acquired immune deficiency syndrome). Pulmonary involvement of MAC may range from asymptomatic colonization of the respiratory tract to invasive parenchymal or cavitary disease. However, endobronchial lesions with MAC infection are rare in immunocompetent and immunosuppressed hosts. Here, we report MAC infection presenting as an endobronchial mass in a patient with AIDS.

Three cases of pulmonary and/or intestinal tuberculosis in adolescents

Since the tuberculosis (TB) in adolescents has unique clinical characteristics, special attention should be paid to this age group. Adolescents are more susceptible to developing TB disease and more likely to have cavitary pulmonary disease. Also, adolescent patients with TB more frequently present with extrapulmonary disease. We report three adolescents with active pulmonary and/or intestinal TB: one had pulmonary and intestinal TB, another had a pulmonary TB, and the third exclusively had an intestinal TB. Diagnosis was confirmed by pathologic examination of the lung and/or intestines. All three patients were treated successfully without complication. A brief review of the literature has been included.

Is Alcohol Use Associated With Cavitary Disease in Tuberculosis?

Alcohol mediates detrimental alterations in the immune response to Mycobacterium tuberculosis. The association between quantity and frequency of alcohol use and the prevalence of cavitary disease in tuberculosis (TB) has not been analyzed. To investigate the relationship of alcohol use and the prevalence of cavitary disease in a 6-year population-based data set of individuals with TB. We assessed quantity and frequency of alcohol use (daily alcohol use, years of alcohol use, and lifetime alcohol use) with a standardized questionnaire. The study group consisted of 1,250 patients analyzed for cavitary disease (HIV sero-negative subjects that were 18 years or older). Significant covariates for cavitary disease were entered into multiple logistic regression models. Although daily alcohol use, years of alcohol use, and alcohol use 30 days or 6 months before symptom onset were significant predictors of cavitary disease in univariate analysis, no independent associations were found between alcohol use and cavitary disease in the multivariate analysis. Only diabetes mellitus was independently associated with cavitary disease at any level or frequency of alcohol use. Alcohol use is not independently associated with increased prevalence of cavitary disease in adult patients with TB.

Factors influencing sputum smear and culture conversion time among patients with new case pulmonary tuberculosis

Sputum smear and culture conversion are important indicators for the effectiveness of treatment and the infectivity of the patient. The aim of this study was to identify the factors influencing both sputum smear and culture conversion time among patients with new case pulmonary tuberculosis (TB). The study was conducted in a reference hospital in Turkey in which 737 patients with pulmonary TB were hospitalised between January 2000 and 2005. We evaluated 306 (193 men and 113 women) human immunodeficiency virus-negative patients diagnosed with new case pulmonary TB. Factors associated with both sputum smear and culture conversion time (days) were investigated. Patients with diabetes mellitus (DM), cavitary disease, radiologically extensive disease had longer sputum smear and culture conversion time than the other groups. In addition, old age, male sex, smoking and thrombocytosis were found to be significantly associated with sputum smear conversion time. In the logistic regression analysis, the presence of DM and extensive disease were determined as independent factors associated with persistent sputum smear and culture positivity at the end of 2 months. The presence of DM and extensive disease were found to be independent risk factors influencing both sputum smear and culture conversion time in pulmonary TB. Sputum smear and culture examinations should be considered together to assess the poor prognosis.

Coccidioidomycosis in Patients with Diabetes Mellitus

Purpose The study reviewed the interrelationships of diabetes mellitus and coccidioidomycosis. Subjects and methods We conducted a retrospective review of the medical records of immunocompetent patients with coccidioidomycosis who were treated at our academic medical institution between January 1, 1999, and October 31, 2003, to compare those with and without diabetes mellitus and to determine whether glycemia correlates with the course of illness. Results Of 329 immunocompetent patients with coccidioidomycosis, 44 had diabetes (4 type 1 and 40 type 2) and were divided into 2 groups: those with serum glucose concentrations of less than 12.2 mmol/L (220 mg/dL) and those with glucose concentrations of greater than or equal to 12.2 mmol/L (220 mg/dL). Persons with diabetes in either glucose group were more likely than those without diabetes to have cavitary lung disease (relative risk, 2.94; P<.001) and relapsed infection. However, only the diabetes group with serum glucose concentrations greater than or equal to 12.2 mmol/L (220 mg/dL) were more likely to have disseminated infection (relative risk, 2.8; P=.05) and to require treatment (relative risk, 9.85; P=.005), but their infection was less likely to resolve (relative risk, 0.24; P=.002). Conclusion Because glycemia strongly correlated with clinical characteristics of coccidioidomycosis in this cohort, we recommend routine measurement of serum glucose in persons with coccidioidomycosis to identify patients with an increased risk of complicated infection. Future studies should evaluate the efficacy of tight glycemic control on the outcome of coccidioidal infection.

Clinical and Molecular Analysis of Macrolide Resistance in Mycobacterium avium Complex Lung Disease

The clinical features and outcome of macrolide-resistant Mycobacterium avium complex (MAC) lung disease are not known. Characterize patients, treatment, and isolates in macrolide-resistant MAC lung disease. Retrospective chart review, susceptibility testing, molecular fingerprinting, and DNA sequence analyses of resistant MAC isolates. We identified 51 patients over a 15-yr period with clarithromycin-resistant MAC (minimum inhibitory concentration (MIC)>or=32 microg/ml) lung disease at a single referral center. Twenty-four (47%) patients had nodular disease with bronchiectasis and 27 (53%) had upper lobe cavitary disease. Most patients (77%) had M. intracellulare. Sequencing of the 23S r-RNA gene showed 49 of 51 isolates (96%) with the expected mutation in adenine 2058 or 2059. Risk factors for resistance included macrolide monotherapy or combination with a quinolone only (39/51 or 76%). Macrolide resistance developed in 12 of 303 (4.0%) patients started on the American Thoracic Society-recommended two companion drugs, with no risk difference in clarithromycin versus azithromycin and daily versus intermittent therapy. Sputum conversion with macrolide-resistant MAC occurred in 11 of 14 (79%) patients who received more than 6 mo of injectable aminoglycoside therapy and lung resection, compared with 2 of 37 (5%) who did not. The 1-yr mortality in patients who remained culture positive was 34% (13/38) compared with 0% (0/13) of patients who became culture negative (converted). Macrolide resistance rarely occurs in patients also receiving ethambutol and a rifamycin. Macrolide-resistant MAC lung disease requires aggressive drug and surgical therapy for cure.

Community-Based Therapy for Children With Multidrug-Resistant Tuberculosis

The goals were to describe the management of multidrug-resistant tuberculosis among children, to examine the tolerability of second-line antituberculosis agents among children, and to report the outcomes of children treated for multidrug-resistant tuberculosis in poor urban communities in Lima, Peru, a city with high tuberculosis prevalence. A retrospective analysis of data for 38 children <15 years of age with multidrug-resistant tuberculosis, either documented with drug sensitivity testing of the child's tuberculosis isolate or suspected on the basis of the presence of clinical symptoms for a child with a household contact with documented multidrug-resistant tuberculosis, was performed. All 38 children initiated a supervised individualized treatment regimen for multidrug-resistant tuberculosis between July 1999 and July 2003. Each child received 18 to 24 months of therapy with > or =5 first- or second-line drugs to which their Mycobacterium tuberculosis strain was presumed to be sensitive. Forty-five percent of the children had malnutrition or anemia at the time of diagnosis, 29% had severe radiographic findings (defined as bilateral or cavitary disease), and 13% had extrapulmonary disease. Forty-five percent of the children were hospitalized initially because of the severity of illness. Adverse events were observed for 42% of the children, but no events required suspension of therapy for >5 days. Ninety-five percent of the children (36 of 38 children) achieved cures or probable cures, 1 child (2.5%) died, and 1 child (2.5%) defaulted from therapy. Multidrug-resistant tuberculosis disease among children can be treated successfully in resource-poor settings. Treatment is well tolerated by children, and severe adverse events with second-line agents are rare.

Digital clubbing in tuberculosis – relationship to HIV infection, extent of disease and hypoalbuminemia

BackgroundDigital clubbing is a sign of chest disease known since the time of Hippocrates. Its association with tuberculosis (TB) has not been well studied, particularly in Africa where TB is common. The prevalence of clubbing in patients with pulmonary TB and its association with Human Immunodeficiency Virus (HIV), severity of disease, and nutritional status was assessed.MethodsA cross-sectional study was carried out among patients with smear-positive TB recruited consecutively from the medical and TB wards and outpatient clinics at a public hospital in Uganda. The presence of clubbing was assessed by clinical signs and measurement of the ratio of the distal and inter-phalangeal diameters (DPD/IPD) of both index fingers. Clubbing was defined as a ratio > 1.0. Chest radiograph, serum albumin and HIV testing were done.ResultsTwo hundred patients (82% HIV-infected) participated; 34% had clubbing by clinical criteria whilst 30% had clubbing based on DPD/IPD ratio. Smear grade, extensive or cavitary disease, early versus late HIV disease, and hypoalbuminemia were not associated with clubbing. Clubbing was more common among patients with a lower Karnofsky performance scale score or with prior TB.ConclusionClubbing occurs in up to one-third of Ugandan patients with pulmonary TB. Clubbing was not associated with stage of HIV infection, extensive disease or hypoalbuminemia.