Diffuse panbronchiolitis in a Caucasian man in Canada.

Diffuse panbronchiolitis (DPB) is a rare, chronic bronchiolar disease in non-Asian populations and is therefore commonly overlooked in Western countries. It usually affects nonsmokers and manifests as persistent air flow obstruction, chronic cough and interstitial nodular opacities. Untreated, the prognosis is poor. In this report the authors describe a Caucasian man of Canadian descent who presented with progressive clinical and lung function impairment despite three years of bronchodilator and corticosteroid treatment with presumed asthma. His chest computed tomography scan showed diffuse centrilobular opacities. Lung biopsy revealed chronic bronchiolitis characterized by infiltration of lymphocytes, plasma cells and foam cells in respiratory and terminal bronchioles, compatible with a diagnosis of DPB. After two months of therapy with clarithromycin, the patient had already shown improvement. Physicians should be aware that DPB may occur in Western countries, and that DPB should be considered in the differential diagnosis of patients with persistent air flow obstruction and nodular shadows on chest radiograms.

Inhaled beclomethasone dipropionate improves acoustic measures of voice in patients with asthma.

BACKGROUND: Inhaled corticosteroids have the potential to produce upper-airway side effects such as hoarseness. As new compounds and delivery devices are developed and compared, it is difficult to quantify their adverse upper-airway effects. OBJECTIVE: We undertook the following study to test the ability of an acoustic analysis technique to quantify changes in vocal function in steroid-naive patients with asthma who receive inhaled beclomethasone dipropionate (BDP), 1,000 microg/d for 4 months. METHODS: Patients self-administered one of four regimens of inhaled BDP. Group 1 patients received one 250-microg puff qid via metered-dose inhaler (MDI); group 2 patients received one 250-microg puff qid via MDI with a holding chamber; group 3 patients received two 250-microg puffs bid via MDI; and group 4 patients received two 250-microg puffs bid via MDI with a holding chamber. A smaller cohort of nonsmoking asthmatic patients was managed without steroid intervention for 4 months. At baseline and again at 8 weeks and 16 weeks after the initiation of BDP treatment, patients underwent spirometry and methacholine challenge. At baseline and again at 2, 4, 8, 12, and 16 weeks, patients underwent voice recording for analysis of voice parameters. The recorded vowels were low-pass filtered (10 KHz), digitized (22 KHz), and analyzed by software to obtain two acoustic measures: (1) jitter, the cycle-to-cycle variation in the time period of the voice signal; and (2) shimmer, the cycle-to-cycle variation in voice signal amplitude. RESULTS: We recruited 77 patients for randomization to inhaled steroid therapy and 10 patients who continued to receive only occasional inhaled bronchodilator therapy. In all active treatment groups, FEV(1), FVC, and provocative concentration of methacholine causing a 20% fall in FEV(1) improved significantly after BDP treatment. Mean jitter scores, a measurement of variation in voice pitch, were not significantly influenced by BDP treatment. However, mean shimmer scores, a reflection of perturbation in vocal amplitude, fell significantly (p < 0.05) in the active treatment groups. These reductions in shimmer scores were not significantly different in the active treatment groups. Shimmer scores in the bronchodilator-treated group were unchanged during the 16 weeks of follow-up. CONCLUSIONS: Our data show that a simple and noninvasive acoustic analysis of voice is sensitive to subclinical changes associated with inhaled corticosteroid therapy. We have shown that 1,000 microg/d of inhaled BDP actually improves specific acoustic measures of voice in patients with inadequately controlled asthma. These improvements were uninfluenced by dosing schedule and whether a spacing chamber was used.

Hypersensitivity pneumonitis with normal high resolution computed tomography scans.

A case of symptomatic hypersensitivity pneumonitis with normal high resolution computed tomography (CT) scans is presented. The patient, a 32-year-old man with systemic lupus erythematosus, had a chronic, progressive history of respiratory symptoms, abnormal findings on examination and abnormal pulmonary function tests but normal high resolution CT scans of the chest. Diagnosis was made through open lung biopsy. Clinical improvement was seen on removal of the offending antigen. The literature on the utility of high resolution CT scans in hypersensitivity pneumonitis is reviewed.

Albuterol via Turbuhaler versus albuterol via pressurized metered-dose inhaler in asthma.

BACKGROUND: Inhaled albuterol is most commonly self-administered by patients using a pressurized metered-dose inhaler (pMDI) but patients often have difficulty using the device. Dry powder devices such as the multi-dose, inspiratory flow driven inhaler (Turbuhaler) are often better handled by patients. OBJECTIVE: We sought to compare the efficacy and tolerability of 100 micrograms of albuterol delivered by a multi-dose, inspiratory flow driven inhaler (Turbuhaler) to a standard dose (200 micrograms) delivered by a pMDI (Ventolin) in chronic reversible obstructive airways disease. METHOD: In 6 centers, we studied 37 adults [19 men and 18 women, mean age 39 +/- 12 years; mean baseline forced expiratory volume in one second (FEV1) 72 +/- 13% (% predicted)] with stable but symptomatic reversible obstructive airways disease as demonstrated by 15% or greater increase in FEV1 following two puffs (200 micrograms) albuterol by pMDI. The crossover design comprised a 1-week run-in and two 2-week treatment periods separated by a 1-week washout. At the start and end of each treatment period, FEV1 was measured at the clinic. Patients self-administered albuterol 100 micrograms (2 x 50 micrograms) via Turbuhaler or 200 micrograms (2 x 100 micrograms) via pMDI in a double-blind fashion four times daily. Morning and evening peak expiratory flow (PEF) was noted daily. All non-study bronchodilators were withheld while open-label albuterol pMDI was offered for rescue. RESULTS: Of the 37 patients, 30 used inhaled steroids in constant doses throughout the study, one used inhaled cromoglycate and six used no anti-inflammatory therapy. There was no difference between treatment periods in morning PEF, diurnal fluctuation in PEF, increase in PEF following study drug, baseline FEV1 and FEV1 increase following study drug. Although there was no difference in symptom scores between treatments, the use of rescue beta 2-agonist was slightly but significantly higher during the Turbuhaler treatment period (1.34 versus 1.08 inhalations/ day, P = .04). Compliance with study drug was slightly but significantly lower during the Turbuhaler treatment period (87 versus 95%) such that the total number of beta 2-agonist puffs inhaled (scheduled plus rescue) was similar between treatments. With regard to adverse events, both treatments were well tolerated. CONCLUSIONS: These results suggest that the efficacy and tolerability of albuterol 100 micrograms qid inhaled via Turbuhaler is similar to albuterol 200 micrograms qid, inhaled via pMDI in stable reversible obstructive airways disease.

Prognosis in a patient with an initial normal pulmonary angiogram.

A 58-year-old man with pleuritic chest pain and an indeterminate lung scan had normal results of Duplex ultrasound studies of the lower limbs and a normal pulmonary angiogram. Recurrent symptoms led to repeated pulmonary angiography and a diagnosis of pulmonary embolism. This case emphasizes the possibility of missing an initial, or developing a subsequent, pulmonary embolism despite a normal angiogram and reinforces the need for serial studies if a noninvasive strategy for the diagnosis of pulmonary embolism is to be employed.

Rapid pulmonary phospholipid accumulation induced by intravenous amiodarone.

Amiodarone causes accumulation of phospholipids in lung alveolar cells, and this phospholipidosis invariably is present when amiodarone pulmonary toxicity is recognized. This effect has usually been demonstrated in patients following several months of therapy. The authors report the occurrence of pulmonary phospholipidosis, diagnosed by bronchoalveolar lavage, six days after commencing intravenous amiodarone therapy.

Cavitary aspergillosis as a complication of AIDS.

The authors report the radiographic findings in two patients with the human immunodeficiency virus (HIV) who presented with cavitary lung disease caused by Aspergillus. Recognition of the disease in one of the patients led to successful medical therapy. Disease due to Aspergillus must be considered in HIV-positive patients with cystic or cavitary disease appearing in chest radiographs.

Erythropoietin response to acute hypoxemia in patients with chronic pulmonary disease.

Chronic hypoxemia is associated with development of secondary polycythemia. To evaluate effects of transient hypoxemia on serum EPO activity in patients with chronic lung disease, we studied six oxygen-dependent patients who underwent either a 4-h oxygen withdrawal or their routine therapy, in a randomized, blinded fashion, on two separate days. Serum EPO did not differ at baseline between study days. Erythropoietin levels did not change significantly over time during normoxic conditions. Under hypoxic conditions, serum EPO levels rose over 4 h with the change from baseline first becoming significant at 2 h. The log of serum EPO response showed an inverse correlation with the level of arterial oxygen saturation. We conclude that patients with chronic lung disease are able to produce EPO in response to acute hypoxemic stress. Transient episodes of hypoxemia, such as occur during sleep or exercise, may result in increased red blood cell production stimulated by this EPO response.

Cocaine induced eosinophilic lung disease.

A patient developed fever, bronchoconstriction, hypoxaemia, pulmonary infiltrates, and serum and bronchoalveolar lavage fluid eosinophilia on two occasions after inhaling crack cocaine. Transbronchial biopsy specimens showed normal lung parenchyma but a dense eosinophilic infiltrate within the bronchial wall. Both episodes resolved promptly after treatment with corticosteroids. Eosinophilic lung disease may be a steroid responsive complication of crack cocaine abuse.

Effects of oxygen withdrawal on catecholamine release in patients on home oxygen therapy.

1. Long-term oxygen therapy in appropriate patients prolongs survival and corrects neuropsychological function. Some tests of mental function paradoxically improve during short periods of oxygen withdrawal in patients on long-term oxygen therapy, although the mechanism of this response is unknown. 2. To evaluate the effects of transient hypoxaemia on plasma adrenaline and noradrenaline levels, we studied eight oxygen-dependent patients who underwent either a 4 h period of oxygen withdrawal or their routine therapy, in a randomized, blinded fashion, on 2 separate days. 3. Plasma noradrenaline did not differ at baseline between study days. During normoxic conditions, plasma noradrenaline levels did not increase significantly with time. By contrast, under hypoxic conditions, plasma levels of noradrenaline rose significantly from 0 to 4 h (P less than 0.05). The magnitude of the noradrenaline response was correlated with baseline noradrenaline such that subjects with the highest resting levels had the largest increase during hypoxia (r = 0.95, P less than 0.001). 4. Plasma adrenaline did not differ at baseline between study days and there were no significant effects of hypoxia on plasma adrenaline levels. 5. We conclude that the sympathetic nervous system, but not the adrenal medulla, is stimulated in chronically oxygen-dependent subjects made acutely hypoxaemic. The magnitude of this stimulation appears to be related to the state of sympathetic nervous system activity at baseline. Improvement in some tests of mental function during transient periods of oxygen withdrawal may be due to non-specific arousal caused by a catecholamine surge.

Haemophilus influenzae abscess presenting as an asymptomatic lung mass.

We report the radiographic and computed tomographic findings in an asymptomatic patient who had a Haemophilus influenzae lung abscess. The diagnosis was made by Gram's staining and culture of abscess material obtained by transthoracic needle aspiration. The radiographic abnormalities cleared after specific antimicrobial therapy.

Multiple defects in arachidonate metabolism in alveolar macrophages from young asymptomatic smokers.

This study was undertaken to localize and determine the relative importance of potential biochemical defects in the release and metabolism of arachidonic acid (AA) in alveolar macrophages (AMs) from asymptomatic smokers. Using high-performance liquid chromatography and radioimmunoassay, we compared the metabolism of both endogenously released and exogenously supplied AA in AMs and autologous peripheral blood monocytes (PBMs) from nine healthy nonsmokers and eight healthy smokers. AMs from both groups incorporated similar amounts of radiolabeled AA into cellular lipids. However, AMs from smokers released only about half as much radioactivity as free AA and its metabolites in response to ionophore A23187, when compared to cells from nonsmokers; this suggests that net phospholipase activity was decreased in smokers. In addition, AMs from smokers synthesized less of total cyclooxygenase and 5-lipoxygenase products than did cells from nonsmokers, both constitutively and in response to A23187 as well as the particulate agonist zymosan. Furthermore the metabolism of exogenous AA to both cyclooxygenase and 5-lipoxygenase products was reduced in smoker cells compared to nonsmoker cells. Inverse relationships between eicosanoid synthesis and intensity of smoking were observed. No differences between smoker and nonsmoker PBMs were found. These results show that the major defect in smoker AMs is at the phospholipase level, with additional defects being present at the levels of the cyclooxygenase and 5-lipoxygenase pathways. All these abnormalities are compartmentalized to the mononuclear phagocyte population of the lung.

Treatment of the recalcitrant asthmatic.

Treatment of "difficult" asthma requires good doctor-patient communication, patient education, and attention to precipitating factors as well as an aggressive drug regimen. Specific medications include inhaled sympathomimetic and anti-cholinergic bronchodilators, inhaled, oral and/or intravenous corticosteroids and, in certain circumstances, mast cell stabilizing drugs such as cromolyn sodium. The use of systemic theophyllines is currently undergoing critical reevaluation. There have been a number of recent developments in the search for steroid-sparing agents and drugs that inhibit inflammatory mediators felt to be important in the pathophysiology of asthma. Most of these drugs are still undergoing evaluation in multicentre clinical trials. The newer antiinflammatory agents, methotrexate and gold, should probably not be used on a routine basis except as part of randomized, ethically approved clinical trials.

Different patterns of arachidonate metabolism in autologous human blood monocytes and alveolar macrophages.

As peripheral blood monocytes (PBM) differentiate into tissue macrophages, they undergo a variety of functional changes. One such difference which has been described is an enhanced metabolism of arachidonic acid (AA) via the 5-lipoxygenase (5-LO) pathway in alveolar macrophages (AM) as compared to PBM. In order to elucidate a possible mechanism for this difference, we compared the metabolism of endogenously released AA mobilized by agonists and of exogenously supplied fatty acid in adherent autologous PBM and AM obtained from six normal subjects. Exogenous AA was metabolized to larger amounts of both cyclooxygenase (CO) and 5-LO products by PBM as compared with AM. Although the two cell types released similar amounts of endogenous AA in response to ionophore A23187, marked differences in the pattern of its metabolism were observed. In PBM, a large proportion of released AA remained unmetabolized, and that which was metabolized was converted predominantly to CO products. In contrast, arachidonate released by AM was efficiently metabolized, predominantly via the 5-LO pathway. Similar results were obtained when cells were stimulated with the particulate zymosan, with PBM synthesizing mainly CO and AM, mainly 5-LO eicosanoids. In addition, culture of PBM for up to 5 days in an aerobic environment did not alter their response to A23187 stimulation. These results suggest that the lesser 5-LO metabolism by PBM than AM is not explained by lesser phospholipase or 5-LO activities, but rather a compartmentalization of the endogenous AA deacylated by phospholipase and the 5-LO enzyme in the PBM. The acquisition of the capacity to metabolize endogenous AA to large quantities of 5-LO products as mononuclear phagocytes differentiate in the lung may equip them with the ability to mount an inflammatory response in the alveolar space.

Arachidonic acid metabolism in cultured alveolar macrophages from normal, atopic, and asthmatic subjects.

In order to test the hypothesis that alveolar macrophages (AM) from asthmatics might manifest abnormalities in the amounts, spectrum, or glucocorticoid regulation of eicosanoid synthesis, we compared arachidonic acid (AA) metabolism under resting and ionophore A23187-stimulated conditions in cultured AM obtained by bronchoalveolar lavage from 10 asthmatic, nine atopic, and 10 nonatopic normal subjects. [14C]AA-prelabeled AM constitutively released free [14C]AA and release increased significantly with A23187 incubation. Under resting conditions, unlabeled cells produced small amounts of immunoreactive thromboxane B2 (TxB2), prostaglandin D2 (PGD2), prostaglandin E2 (PGE2), and leukotriene B4 (LTB4). With A23187 stimulation there were significant increases in the synthesis of all immunoreactive metabolites, which were produced in the following relative amounts: LTB4 much greater than TxB2 greater than PGD2 greater than leukotriene C4 greater than PGE2. High performance liquid chromatographic separation of radiolabeled eicosanoids produced by prelabeled cells confirmed the radioimmunoassay results and further indicated the production of relatively large amounts of 5-hydroxyeicosatetraenoic acid and 12-hydroxyheptadecatrienoic acid. Pretreatment (16 h) with 1 microM methylprednisolone inhibited A23187-induced synthesis of immunoreactive cyclooxygenase products to a greater extent than immunoreactive leukotrienes. We identified no significant differences among the three study groups in the quantities or profiles of eicosanoids synthesized either constitutively or with A23187 stimulation, nor in their regulation by methylprednisolone.