Charles P. Andrews

Aspergillus antigen detection in bronchoalveolar lavage fluid from patients with invasive aspergillosis and aspergillomas

Improved diagnostic techniques have been needed for pulmonary aspergillosis, a common opportunistic fungal infection with a high mortality rate. Radioimmunoassay was used in this study to detect Aspergillus antigen in bronchoalveolar lavage fluid. In four patients with invasive aspergillosis or aspergillomas, Aspergillus antigen was detected in bronchoalveolar lavage fluid. In two patients, results of fungal cultures were negative or delayed. The specificity of antigen detection in bronchoalveolar lavage fluid was 91 percent in 35 control patients with a variety of pulmonary disorders. The technique or radioimmunoassay detection of microbial antigen in bronchoalveolar lavage fluid appears promising for the diagnosis of aspergillosis.

Responses to ragweed pollen in a pollen challenge chamber versus seasonal exposure identify allergic rhinoconjunctivitis endotypes

BACKGROUND The level of concordance between allergic symptoms induced on exposure to pollen in a pollen challenge chamber (PCC) versus the natural season is unknown. OBJECTIVE We sought to test the hypothesis that the symptom levels of allergic rhinoconjunctivitis elicited after out-of-season exposure to short ragweed in a PCC and during the natural season for giant ragweed pollen are highly correlated. METHODS Thirty-one ragweed-sensitive participants recorded symptoms for 15 days during the natural giant ragweed season in San Antonio, Texas. Twenty-six of these participants were challenged to short ragweed pollen in a PCC for 3 hours per day for up to 4 days. RESULTS In the PCC participants were dichotomized into those in whom low versus high levels of symptoms developed slowly or rapidly (ie, slow/low vs rapid/high). Each successive exposure visit associated with a progressive increase in symptom levels that approximated those experienced during the natural season. Hierarchic clustering identified 3 endotypes: endotypes I and II reflected concordantly low (n= 7) versus high (n = 14) total symptom scores (TSSs) in both the natural season and the PCC, respectively. Accordingly, the correlation between the TSSs recorded in the natural season and in the PCC for these 21 participants was very high. Although participants with endotype III (n = 5) had greater TSSs in the natural season than in the PCC, the degree of correlation between the TSSs remained high. CONCLUSIONS Our findings affirm our hypothesis, underscore the high cross-reactivity between distinct pollens, and highlight the utility of the PCC to identify novel allergy endotypes that might have contrasting mechanistic underpinnings and potentially therapeutic responses.

Comparison of fluticasone propionate aqueous nasal spray and oral montelukast for the treatment of seasonal allergic rhinitis symptoms.

BACKGROUND Few studies have directly compared the efficacy of intranasal corticosteroids with that of leukotriene receptor antagonists for the treatment of daytime and nighttime symptoms of seasonal allergic rhinitis (SAR). OBJECTIVE To compare fluticasone propionate aqueous nasal spray, 200 microg daily, with oral montelukast, 10 mg daily, for the relief of SAR symptoms. METHODS Patients with SAR 15 years or older were randomized to receive either fluticasone propionate (n = 367) or montelukast (n = 369) in this double-blind, double-dummy, parallel-group study. The primary efficacy measure was the mean change from baseline in daytime total nasal symptom scores (TNSSs) (the sum of 4 daytime individual nasal symptom scores [INSSs] assessing nasal congestion, itching, rhinorrhea, and sneezing), averaged across weeks 1 and 2. Secondary efficacy measures included the 4 daytime INSSs, nighttime TNSSs (the sum of 3 nighttime INSSs assessing congestion on awakening, difficulty going to sleep, and nighttime awakenings), and the 3 nighttime INSSs averaged across weeks 1 and 2. RESULTS Mean changes from baseline in daytime TNSSs (P < .001), all daytime INSSs (P < .001), nighttime TNSSs (P < .001), and all nighttime INSSs (P < or = .02) showed significant differences favoring fluticasone propionate over montelukast across 2 weeks of treatment. CONCLUSION Compared with montelukast, fluticasone propionate provided significantly greater improvement in daytime and nighttime SAR symptoms.

Organic antigen-induced interstitial lung disease: diagnosis and management

BACKGROUND Traditionally, chronic idiopathic interstitial pneumonia/fibrosis (IIP/F) had included usual interstitial pneumonia, desquamative interstitial pneumonia, and nonspecific interstitial pneumonia (NSIP). More recent classifications have included bronchiolitis obliterans-organizing pneumonia (BOOP), respiratory bronchiolitis-associated interstitial lung disease, and acute interstitial pneumonia. Some chronic eosinophilic pneumonias (CEP)/pulmonary infiltrate with eosinophilia (PIE) have obvious causes, but many lack an identifiable etiology. We felt that hypersensitivity pneumonitis (HP) was being underdiagnosed and was hidden within this large heterogeneous group of interstitial lung disorders of unrecognized cause. OBJECTIVE We sought to prove that detailed environmental histories and investigations would reveal causative contaminations in the home or workplace of some patients with idiopathic interstitial lung disease and remediation of the contamination would stabilize the disorder. METHODS Consecutive cases of IIP/F were investigated. Patients were identified by compatible signs and symptoms, roentgenographic studies, pulmonary function tests, and lung biopsies. They were further evaluated with detailed environmental histories, serologic tests, and investigation into the suspected causative environment. Environmental and specific antigen challenges were done in some cases. Remediation of contaminations or moving into another environment were the methods used as therapy. RESULTS Eighty-six consecutive patients with IIP/F were evaluated. Twelve patients were subsequently diagnosed with specific causes for interstitial lung disease. Fifty-seven of 74 patients were identified by clinical evaluation and lung biopsy with HP, CEP/PIE, NSIP, BOOP, UIP, and nonclassifiable morphologic patterns. Seventeen patients were not biopsied or had an inadequate transbronchial biopsy but had consistent findings radiographically and clinically of idiopathic interstitial lung disease. Contamination of the home was causative in 69 of 74 and the workplace in 3 of 74 cases. There were 9 positive and 33 negative environmental challenges with 4 positive and 1 negative specific challenges. Fifty of 74 (67%) patients are receiving no treatment and are free of active disease after remediation of the environmental contamination, with a mean survival of 8.2 years. CONCLUSIONS Our data show that UIP, BOOP, NSIP, CEP/PIE, and nonclassifiable morphologic patterns represent a spectrum of interstitial lung disease that may be caused by inhalation of organic dusts in the home or workplace as described with HP. Remediation of, or moving from the contamination, can lead to arrest of the active inflammatory process and stability of the lung disorder.

Hypersensitivity pneumonitis: beyond classic occupational disease–changing concepts of diagnosis and management

OBJECTIVE To review inhaled antigens in home environments that cause hypersensitivity pneumonitis (HP) of varied clinical expressions and histopathologic patterns. DATA SOURCES Computer-assisted MEDLINE and manual searches for articles concerning HP, interstitial lung disease (ILD), epidemiology of HP and ILD, challenge procedures of HP, and indoor fungi. STUDY SELECTION Published articles concerning inhaled antigens in home environments and HP were selected. RESULTS Current criteria for the diagnosis of HP are too restrictive, because most apply only to the classic acute presentation and are of limited value in the subacute and insidious forms. Clinical expressions vary across the gamut of respiratory tract signs and symptoms. Patterns on lung biopsy may include all histopathologic descriptions of idiopathic ILD. The home is the likely causative environment rather than the workplace. Exposures may be occult and require in-depth environmental histories and on-site investigations to detect antigens and sources. CONCLUSIONS Natural or environmental challenges have become an important tool for diagnosing HP and determining effectiveness of remediation. Early diagnosis and effective remediation of the cause lead to a high survival rate, whereas diagnosis in advanced stages leads to disability and/or premature death.

Fluticasone furoate nasal spray is more effective than fexofenadine for nighttime symptoms of seasonal allergy.

Nasal symptoms of allergic rhinitis are an important cause of sleep disturbance. Reduction of nasal symptoms, particularly nasal obstruction, has been linked to improvements in self-reported sleep quality. The enhanced-affinity intranasal corticosteroid fluticasone furoate and the oral antihistamine fexofenadine were compared with respect to nighttime symptoms of seasonal allergic rhinitis. In two randomized, double-blind, double-dummy, parallel-group studies, patients received fluticasone furoate nasal spray (FFNS),110 microg (study 1, n = 312; study 2, n = 224); fexofenadine, 180 mg (study 1, n = 311; study 2, n = 227); or placebo (study 1, n = 313; study 2, n = 229) once daily for 2 weeks. Fluticasone furoate was more effective (p < 0.001) than fexofenadine and placebo in both studies with respect to the mean changes from baseline over the treatment period in the nighttime symptoms score, nighttime reflective total nasal symptom score, predose instantaneous nasal symptom score, and morning peak nasal inspiratory flow. Fluticasone furoate was more effective than placebo (p <or= 0.001) in study 1 and more effective than both placebo and fexofenadine (p <or= 0.034) in study 2 with respect to the mean changes from baseline in the nighttime reflective total ocular symptom score and predose instantaneous total ocular symptom score. In these double-dummy studies, fexofenadine did not separate from placebo in comparisons of the nighttime symptoms score or the nighttime nasal or ocular symptom measures. The incidence of adverse events was similar among groups. FFNS once daily was more effective than fexofenadine and placebo with respect to nighttime sleep disturbance caused by seasonal allergy symptoms.

Acute pulmonary edema associated with use of low-molecular weight dextran for prevention of microvascular thrombosis

Low-molecular weight dextran is commonly used to prevent thrombosis after microvascular procedures; however, the potential complications of this drug are not well known. We report a case of acute pulmonary edema in a healthy person after elective microsurgery for treatment of a malignant tumor of the forearm. The mechanism of action of dextran and the pathophysiology of two potential adverse reactions to this drug are discussed. It is thought that in this patient pulmonary edema was caused by dextran toxicity.

Hypersensitivity Pneumonitis Treated with an Electrostatic Dust Filter

A 60-year-old woman had had recurrent acute migratory pneumonias for 9 months. The results of an evaluation, which included tests for serum precipitins, a transbronchial biopsy, and a bronchial provocation, confirmed a diagnosis of hypersensitivity pneumonitis caused by an Aspergillus species. The findings from gravity air cultures in the home showed a heavy infestation of mold. The installation of electrostatic dust filters in the return ducts of the central air conditioning system resulted in the lowering of mold colony counts to normal levels. This change in the environment enabled the patient to live at home without having the signs and symptoms of hypersensitivity pneumonitis, or a need for medication. Thirty months after the electrostatic dust filters were installed, total mold colony counts were still normal, the patient remained free of the signs and symptoms of hypersensitivity pneumonitis, and serum precipitins could no longer be demonstrated. The results of a bronchial challenge to Aspergillus species, however, remained positive; these positive results suggest that long-term memory immune mechanisms may play an important role in the pathogenesis of hypersensitivity pneumonitis and lessen the importance of precipitins in establishing a diagnosis. We report that electrostatic dust filters may be an effective treatment for patients with hypersensitivity pneumonitis when avoidance of the causative antigen cannot be easily and rapidly achieved.

Effect of confounding cofactors on responses to pollens during natural season versus pollen challenge chamber exposure.

BACKGROUND The severity of allergic rhinoconjunctivitis (AR) symptomatology elicited after exposure to pollen in the absence versus the presence of confounding cofactors, such as in a pollen challenge chamber (PCC) and the natural pollinating season, respectively, might differ. OBJECTIVE We sought to determine the correlation of AR severity in the natural season versus out-of-season PCC exposures. METHODS Twenty-four Virginia live oak (VLO)-positive, 14 VLO-negative, 16 mountain cedar (MC)-positive, 8 MC-negative, and 26 ragweed-positive participants recorded AR symptoms (total symptom score [TSS]) during the VLO, MC, and ragweed pollinating seasons and during 2 consecutive PCC exposures of 3 hours each to these pollens separately. RESULTS The TSSs recorded before the natural season were higher than the pre-PCC values. This prepriming was greater among VLO(+) than MC(+) participants, and it blunted further increases in TSSs during the VLO natural season. Nonatopic participants were nonreactive in the PCC. There was wide variation in the level of AR symptomatology after exposure to VLO, MC, or ragweed pollen in the PCC. Prepriming formed the basis for higher AR responses observed in the natural season than in the PCC, resulting in the identification of distinct PCC/natural season endophenotypes and a partial correlation between the TSSs recorded in the natural season versus those recorded in the PCC (r = 0.34, 0.54, and 0.65 for VLO(+), MC(+), and ragweed-positive participants, respectively). CONCLUSIONS Prepriming in the natural pollinating season might obscure the true correlation between AR severity in the natural season versus the PCC. By mitigating confounding cofactors, PCC exposures have utility for evaluation of novel AR therapeutics.

Hypersensitivity pneumonia–nonspecific interstitial pneumonia/fibrosis histopathologic presentation: a study in diagnosis and long-term management

BACKGROUND Nonspecific interstitial pneumonia/fibrosis (NSIP) has been classified a form of idiopathic interstitial pneumonia/fibrosis. We have shown that cases of NSIP without demonstrable serum precipitins may be caused by inhalation of high levels of mold and/or bacteria in closed environments. OBJECTIVE We report a patient with a clinical and histopathologic diagnosis of NSIP without serum precipitins caused by a microbial contamination in her home. Her case was converted from an acute to an insidious clinical presentation by inadequate remediation. A prolonged avoidance-challenge technique demonstrated that this case of NSIP was a form of hypersensitivity pneumonia that was reversible by effective remediation. METHODS The patient was identified by compatible signs and symptoms, roentgenographic studies, pulmonary function tests, and a transbronchial lung biopsy. She was further evaluated with a detailed environmental history, serologic tests, and investigation of the home environment. An environmental avoidance and challenge technique was performed to confirm cause and effect and to determine that remediation had been effective. RESULTS Review of the biopsy showed NSIP and failed to reveal any non-caseating granuloma formation. Investigation of the home revealed a Cladosporium species contamination of the air conditioning system and Penicillium species beneath an entryway carpet. Serum precipitins to commercial antigens of common mold to the south Texas area were negative. Avoidance and challenge techniques confirmed the home as the causative environment in this case of NSIP. The patient has been free of signs and symptoms and has taken no medication for interstitial lung disease over the past 30 months. CONCLUSIONS Some cases of NSIP may be caused by inhalation of microbial antigen(s) in a closed environment. An environmental challenge technique was an effective method to determine the causative environment and confirm that remediation had been effective. Inadequate remediation may lead to symptomatic improvement, but may convert a patient from an acute to an insidious presenter. The environmental challenge obviates a need for specific challenges to determine specific causation. Remediation of or moving from an environmental contamination to achieve reversibility or prevent progression was the treatment of choice to avoid use of long-term immunosuppressive agents.