Beclomethasone diproprionate reduced airway inflammation without adrenal suppression in young children with cystic fibrosis: a pilot study.

Inhaled corticosteroids are commonly used in cystic fibrosis (CF), but there are few studies evaluating their safety in young children. We, therefore, prospectively administered beclomethasone diproprionate (BDP) to 12 clinically stable young children with CF to examine the safety of this therapy with respect to adrenal suppression and airway infection. To determine potential mechanisms of corticosteroid action in CF, we also examined airway markers of inflammation before and after inhaled steroid treatment. BDP 210 microg twice a day was given via spacer for 2 months. Twelve-hour serum and urine cortisols and response to low-dose synthetic ACTH cortisol stimulation were assessed. Bronchoalveolar lavage fluid (BALF) was examined pre- and posttreatment with BDP by quantitative bacteriology and indices of airway inflammation, including levels of total neutrophils, neutrophil elastase-alpha-1 antiprotease complexes (NEAP), CA 19-9 mucin-associated antigen, interleukin-8 (IL-8), and macrophage IL-8 mRNA. Following 2 months of treatment, serum and urine cortisol levels were unchanged. Response to low-dose ACTH cortisol stimulation was not significantly decreased at 30 min. Posttreatment BALF bacterial density was not statistically different from pretreatment; however, one patient who was initially culture negative became culture-positive with Hemophilus influenzae. BALF total neutrophil counts, corrected for epithelial lining fluid dilution, were decreased to approximately one third of pretreatment values (P = 0.03). NEAP and CA 19-9 mucin-associated antigen demonstrated similar decreases. BALF IL-8 levels and macrophage IL-8 mRNA levels were not statistically changed. These findings suggest that treatment with BDP 420 microg per day for 2 months in young children with CF does not affect urine and blood cortisol, causes no decrease in adrenal reserve, and does not result in a clinically significant increase in airway infection. In addition, the fall in bronchoalveolar lavage fluid inflammatory markers following BDP suggests possible modulation of neutrophil influx into the CF airway and provides justification for further studies of inhaled corticosteroids in CF.

Clinical efficacy and cost benefit of pulse flow oxygen in hospitalized patients.

Pulse flow oxygen administered during early inspiration is a promising approach to oxygen conservation. Previous short-term studies show equivalent arterial PO2, 55 to 60 percent oxygen savings, and no reduction of nasal humidity when compared with continuous flow nasal cannula oxygen. This study compares the clinical efficacy of pulse flow and continuous flow oxygen in 100 patients recently hospitalized for diseases requiring O2 therapy. In an unblinded crossover design, pulse and continuous O2 were administered alternately during four 51/2-hour periods. Oxygen saturation was monitored continuously during the 23-hour study. Mean SaO2 on pulse flow (95.6 +/- 2.7 percent) was clinically the same as continuous flow (95.3 +/- 2.6 percent). Mean SaO2 on pulse flow during the 30 minutes before or after each crossover (95.5 +/- 3.3 percent) was similar to continuous flow during the 30 minutes near crossover (95.3 +/- 3.1 percent). It is concluded that the two delivery systems produce similar levels of SaO2 over the course of a day and night. Analysis of potential cost savings achieved by use of the device for a 350-bed hospital suggests a savings of about $50,000 yearly when accompanied by termination of oxygen humidification.

Is routine assessment of arterial oxygen saturation in pulmonary outpatients indicated?

Pulse oximetry was used in 1,675 pulmonary outpatient visits to determine whether routine assessment of arterial oxygen saturation was indicated in detecting unanticipated severe desaturation. An SaO2 less than 85 percent was found in only 18 visits (1.1 percent). Changes in symptoms, pulmonary function or both which alerted the clinician to a possible problem were identified in 16 of those 18 visits. Only two episodes of desaturation were not identified by history or simple spirometric evaluation. Routine pulse oximetry does not appear to be of value in screening large numbers of pulmonary outpatients for unexpected desaturation, since it is uncommon in the absence of associated clinical findings.

Breathing pattern abnormalities and arterial oxygen desaturation during sleep in the congestive heart failure syndrome. Improvement following medical therapy.

We observed breathing pattern abnormalities and arterial oxygen desaturation in patients with stable congestive heart failure during overnight polysomnography. To determine whether congestive heart failure was the reason for these abnormalities, we then studied six additional patients before and after treatment of heart failure. Breathing was more abnormal (153 +/- 87 episodes/night) during decompensation of heart failure and improved with medical therapy (72 +/- 100 episodes/night) (p less than 0.05). Abnormal breathing patterns resolved in three patients, improved in two, and were unchanged in one patient after therapy. Allographic cardiac transplantation in one patient whose sleep study remained unchanged after medical therapy was associated with resolution of breathing pattern abnormalities and severe desaturation during sleep. Therapy-related improvement in nocturnal respiratory events suggests congestive heart failure is a contributing factor for breathing abnormalities and arterial oxygen desaturation during sleep.

Nocturnal positive pressure ventilation via nasal mask.

Five patients with chronic respiratory failure from neuromuscular disease and symptomatic worsening nocturnal hypoventilation were treated with nocturnal ventilation. Home ventilation at night was provided by a volume-cycled positive pressure ventilator attached to a nasal mask originally designed to administer nasal continuous positive airway pressure (CPAP) for obstructive sleep apnea. The device was well tolerated. Symptoms of headache, insomnia/somnolence, and impaired intellectual capacity rapidly disappeared with nocturnal ventilatory support. Daytime arterial PO2 and PCO2 improved after therapy. There are several advantages over commonly used, negative pressure devices for nocturnal ventilation. These include patient synchronization of tidal volume, ease of application, less cumbersome apparatus, more nocturnal patient mobility, and absence of production of upper airway obstruction.

Treatment of central nervous system sarcoidosis with radiotherapy.

This report documents the twelve-year follow-up of a patient with neurosarcoidosis with multiple progressive central nervous system manifestations. Increased somnolence and seizure activity were associated with proliferation of nodular enhancing brain lesions, as seen on serial computed tomographic (CT) scans. Initially he responded to corticosteroid treatment, but gradually this response became unsatisfactory. After whole-brain irradiation with a total dose of 3,000 rads, his clinical symptoms improved with disappearance of the enhancing brain lesions seen on CT scan.

Hypercapnia during weaning. A complication of nutritional support.

Excess carbohydrate calories in total parenteral nutrition (TPN) solutions can precipitate acute hypercapnic respiratory failure in patients with chronic lung disease secondary to increased carbon dioxide (CO2) production. Two young patients recovering from the adult respiratory distress syndrome experienced hypercapnia during weaning as a result of nutritionally related increased CO2 production. As carbohydrate calories were decreased, CO2 production diminished and hypercapnia resolved. Hypercapnia as a complication of nutritional support during weaning can occur in patients without chronic lung disease and is corrected by decreasing carbohydrate calories.

Effect of location, pH, and temperature of instillate in bronchoalveolar lavage in normal volunteers.

Bronchoalveolar lavage has not been subjected to careful standardization. We examined the variables of lung lavage location and lavage fluid composition (pH and temperature) upon the percent of fluid recovered, cell count and differential, protein and pH in normal subjects. In the first part of the study, random order lavages of the right middle lobe (RML), right lower lobe (RLL), left lingula, and left lower lobe (LLL) were performed with 100-ml aliquots of normal saline (pH, 5.5) at room temperature (25 degrees C). Percent fluid recovery was greater in the RML and lingula than in the RLL (p less than 0.05). Cell count, cell differential, and protein were similar between lobes. In the second part of the study, each lobe was lavaged with 50-ml aliquots: the RML with normal saline at 37 degrees C, the RLL with normal saline buffered to a pH of 7.0 at 37 degrees C, the left lingula with normal saline at 25 degrees C, and the LLL with normal saline buffered to a pH of 7.0 at 25 degrees C. Percent fluid recovery was greater in the RML than in the lingula and greater in both the RML and lingula than in the lower lobes (p less than 0.05). Total cell count was significantly higher in the RML than in the LLL (p less than 0.05). Cell count per milliliter and protein recovered were not different between any lobe lavaged. The pH of recovered fluid was greater with buffered saline. Complications of fever and chills occurred in almost 50% of subjects in both parts of the study. Lavage location can affect fluid recovery. Alteration of lavage fluid composition did not affect cell or protein recovery. We suggest lavage of the RML to ensure larger fluid recovery and the highest total cell count.

Triamcinolone aerosol. Treatment of aspirin-hypersensitive asthmatic patients.

The efficacy of triamcinolone acetonide aerosol in the management of asthma in six patients with aspirin hypersensitivity was evaluated during a one-year trial. Five patients were previously chronically dependent on systemic corticosteroids and had undergone unsuccessful trials with cromolyn sodium therapy. Substantial reduction in corticosteroid requirements was observed; in two patients, oral prednisone therapy was completely eliminated. Forced expiratory volume and flow were maintained at levels better than those recorded before triamcinolone therapy throughout the year of follow-up. No substantial side effects due to triamcinolone were observed.

Foreign body removal with the flexible fiberoptic bronchoscope.

Intrabronchial foreign bodies are occasionally encountered in adults but most available information in humans consists only of reports evaluating one or two cases. We surveyed our experience and found seven patients with intrabronchial foreign bodies who had been examined with the flexible fiberoptic bronchoscope, six of whom were managed successfully. Nine cases have been identified in the literature. Although there were no major complications in either our cases or those in the literature, several problems were identified which under other circumstances could have caused significant complications. We assessed all of these cases for situations which presented potential risk to the patient. These risks were grouped into the following problem categories: 1. selection of appropriate bronchoscope, 2. availability of appropriate instruments, 3. control of the foreign body, and 4. unexpected foreign bodies. Endoscopists planning to use the FFB in foreign body removal should be aware of the problems and hazards which may ensue if improperly managed, and should attempt to gain experience either in the animal laboratory or in models prior to approaching patients with foreign bodies with the flexible fiberoptic bronchoscope.

Oropharyngeal candidiasis in patients treated with triamcinolone acetonide aerosol.

Thirty asthmatic patients participating in a trial of triamcinolone acetonide aerosol were evaluated to determine the relationships among symptons of sore throat or hoarseness, the appearance of the throat on physical examination, and the presence of yeasts on pharyngeal culture. Observations were recorded prior to aerosol therapy and repeated after 2 wk, 4 wk, 6 wk, 4 mo, and 6 mo of therapy. A total of 15 patients (50%) experienced sore throat or hoarseness, 15 (50%) had yeasts cultured from the pharynx on at least one occasion, and 11 (37%) at some point had an abnormal throat examination; however, there was no predictable relationship between symptoms or abnormal physical examinations and the presence of a positive culture. The frequency of positive cultures did not change significantly during the observation period. Twelve patients had positive yeast cultures on 50% or more of their samples. The incidence of symptoms was not sigficantly increased in these chronically colonized patients. Symptoms were usually transient, and discontinuation of the aerosol or antifungal therapy was unnecessary. Triamcinolone aerosol was not associated with significantly increased pharyngeal colonization with yeasts in this 6-mo study. Existing chronic colonization is not necessarily a contraindication to triamcinolone therapy. Sore throat and hoarseness are usually unrelated to yeast infection in patients using triamcinolone acetonide aerosol.

Cromolyn sodium in the treatment of asthma associated with aspirin hypersensitivity and nasal polyps.

The control of asthma by therapy with cromolyn sodium was studied in 28 adults with late-onset asthma associated with hypersensitivity to aspirin and nasal polyps. Four-week periods of treatment with the drug or a placebo were compared in a double-blind crossover study. A subsequent eight-week open trial in 20 patients was compared to their period of receiving placebo. There was slight but significant improvement in the forced expiratory volume in one second (FEV1; P less than 0.05) and the mean forced expiratory flow during the middle half of the forced vital capacity (FEF25-75%; P less than 0.05) after four weeks of therapy with cromolyn sodium and in the FEV1 (P less than 0.05), the forced vital capacity (P less than 0.01), and FEF25-75% (P less than 0.01) after an additional eight weeks of therapy with cromolyn sodium. The improvement in pulmonary function was not associated with changes in the peak expiratory flow rate, the symptoms of asthma, the doses of additional medication, or the index of disability. The dosage of corticosteroids in 22 patients receiving long-term therapy with steroids was no different between the four-week periods of treatment with placebo or drug but was significantly lower (P less than 0.05) during the eight-week open trial. We conclude that administration of cromolyn sodium has a therapeutic effect in this group of asthmatic patients.

Treatment of allergic aspergillosis with triamcinolone acetonide aerosol.

The successful management of a patient with allergic asperillosis with triamcinolone acetonide for one year is reported. This patient had been maintained previously on systemic attempt to withdraw systemic corticosteroids continuously for eight years. An initial attempt to withdraw systemic steroids after initiation of aerosol therapy was unsuccessful; however, following bronchoscopic removal of mucus plugs, the transfer to maintenance therapy with triamcinolone aerosol alone was uneventful.

Desquamative interstitial pneumonia following long-term nitrofurantoin therapy.

Two patients with diffuse interstitial lung disease after long-term nitrofurantoin therapy were characterized clinically by exertional dyspnea and basilar rales, roentgenographically by diffuse interstitial infiltrate and physiologically by a restrictive lung defect. Pathologically, light microscopy revealed desquamative interstitial pneumonia. In one patient electron microscopy was characteristic of desquamative interstitial pneumonia. Immunofluorescent studies of one biopsy specimen showed specific fluorescence of interstitial cells with immunoglobulin E and third component of complement. In in vitro studies, nitrofurantoin therapy failed to induce lymphoblast transformation or histamine release. Treatment consisted of discontinuing the administration of nitro=furantoin and adding corticosteroids. Both patients felt better and showed clinical improvement. Our findings suggest that in some cases desquamative interstitial pneumonia may be drug related.