Contemporary management of chronic persistent cough.

A chronic persistent cough is one that lasts longer than eight weeks in a patient without known chronic pulmonary disease. These patients may experience prolonged frustration, guilt and self-imposed social isolation, besides risking the medical and surgical complications of recurrent coughing episodes, if the cause of their cough is not quickly established and treated. A comprehensive discussion of the management approach to this problem with reference to the recent literature is presented.

Comparison of six oxygen delivery systems for COPD patients at rest and during exercise.

Five different oxygen-conserving devices were tested in each of ten oxygen-dependent patients with COPD who had met the NOTT criteria for continuous oxygen use. They were tested on room air, their prescribed continuous oxygen flow and then on each of the five devices. The devices which delivered a bolus of oxygen during early inspiration or increased oxygen delivery as the respiratory rate increased did better than those devices which delivered oxygen at a normal flow rate during inspiration or a fixed portion of inspiration. In at least one of the subjects each device was associated with desaturation to less than 80 percent during a 12-min walk. It is concluded that oxygen-conserving devices vary in their ability to maintain SaO2 levels during exercise. It is recommended that a home oxygen evaluation include measurement of an exercise SaO2 utilizing the prescribed oxygen delivery system.

Transdermal delivery of the alpha 2-agonist clonidine does not alter airways responses to inhaled histamine or methacholine.

Previous studies have reported that the inhalation of the alpha 2-agonist clonidine decreases airways reactivity. Other studies have shown that oral doses of clonidine acutely increase airways reactivity to histamine, but not to methacholine. Recently, a transdermal clonidine delivery system (TTS) has been approved for use, and there is an increasing interest in using this system for management of postmenopausal and smoking cessation symptoms. To our knowledge, the effects of TTS on airways function in asthmatics have not been reported. The purpose of this study was to determine if use of TTS would alter airways reactivity. Six asymptomatic asthmatic subjects underwent a baseline methacholine challenge (M). In a double-blinded randomized crossover fashion, either a placebo or a TTS patch (TTS-1, 0.1 mg/day), was applied to the arm. Four days later, the challenge was repeated. After two to three days of washout, the alternate patch was applied, and a second challenge was performed. Several days later, a second baseline challenge was repeated. This sequence was then repeated using histamine (H). The patch was well tolerated by all subjects. There was no significant change in resting pulse or blood pressure, and for the group no change in airways reactivity to either M or H was noted. In conclusion, while use of TTS-1 does not improve airways function, its short-term use in asthmatics is not associated with an increase in airways reactivity.

Comparison of ipratropium bromide and albuterol in chronic obstructive pulmonary disease: a three-center study.

Seventy-two subjects who had severe chronic obstructive pulmonary disease and a history of heavy smoking completed a study to compare the effect of single doses of ipratropium bromide (0.036 mg), albuterol (0.18 mg), and placebo on the forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), heart rate, and blood pressure during a period of 6 hours. During initial testing for reversibility, 40 subjects did not demonstrate a 15% increase in FEV1 from baseline after metaproterenol. Ipratropium produced a significantly greater response than albuterol in FEV1 at 3, 4, and 5 hours and in FVC at 1, 2, 3, 4, and 5 hours. For the entire 6-hour period, ipratropium produced a 25% greater response than albuterol in FEV1 and a 50% greater response in FVC. The difference between the two drugs was even greater between 3 and 6 hours. There were no significant differences between the three treatments as regards adverse reactions, heart rate, and blood pressure measurements. In patients who have chronic obstructive pulmonary disease, ipratropium bromide has apparent benefits over beta 2 agonist therapy, including a longer duration of action. Ipratropium may also be effective when beta 2 agonists are not effective.

Pulmonary perivascular and interstitial inflammation in MRL/MpJ-lpr/lpr mice. III. Modulation by cyclophosphamide and sex hormones in 4- and 6-month-old animals.

Estradiol (E) abolished clearing of pulmonary inflammation in 2-month-old male MRL/MpJ-lpr/lpr (MRL/l) mice treated with cyclophosphamide (CY). To determine if this effect persisted in animals with advanced disease, we studied male and female MRL/l mice, aged 4 and 6 months (4M, 6M, 4F, and 6F, respectively). Mice were treated, beginning at 1 month of age, with saline, CY (12 mg/kg/day), CY + castration, CY + castration + testosterone (T) in females, and CY + castration + E in males. CY had no effect on pulmonary inflammation in 4M, possibly because of the development of relatively mild lesions. However, CY was highly effective in 6M. CY + castration + T significantly reduced overall inflammation in 6F and showed a trend in 4F. CY alone had a variable effect on bronchoalveolar lavage fluid (BALF) cells and BALF IgG in both males and females. However, concurrent treatment with T was required for histologic changes of pulmonary inflammation to fully respond to a high dose of CY in female mice. E-treated males had reduced responsiveness to CY.

A survey of the current use and methods of analysis of bronchoprovocational challenges.

The purpose of this study was to survey the current techniques and methods of analysis in bronchoprovocational challenges currently in use. A questionnaire was sent to 94 investigators who had recently published an article in which a bronchoprovocational technique was used. They were asked to answer questions regarding the techniques used in challenge procedures and to calculate the results of ten histamine challenges which had previously been performed in our laboratory. Forty-four responded; 32 of these gave specific results for the histamine challenge. The most common provocative agent utilized was methacholine (62 percent), and that most used delivery mode was a dosimeter for delivery (55 percent). The most common provocative agent utilized was methacholine (62 percent) and the most used delivery mode was a dosimeter (55 percent).

Corticosteroid treatment of hemolytic anemia associated with Mycoplasma pneumoniae pneumonia.

We have described a 35-year-old man with M pneumoniae pneumonia who had severe hemolytic anemia that appeared to respond well to high-dose corticosteroid therapy. Whether corticosteroids have value in decreasing the severity of hemolytic anemia due to cold agglutinin and other protean extrapulmonary manifestations with M pneumoniae infection needs further controlled study. Our experience suggests that corticosteroids may be beneficial.

Anaphylaxis due to cornstarch surgical glove powder.

Two nurses suffered anaphylaxis to cornstarch glove powder. Both exhibited (1) positive prick skin tests to cornstarch powder in water, with resultant anaphylaxis in one and (2) negative prick skin tests and RAST to corn. Analysis of the powder revealed only glucose and inorganic salts. We were unable to detect in vitro histamine release or cornstarch powder specific IgE. Because of the positive skin tests and the resultant anaphylaxis, we suspect that cornstarch is the responsible allergen.

Absence of tachyphylaxis to inhaled atropine in patients with chronic obstructive pulmonary disease.

A multicenter, 14-wk, double-blind, randomized, parallel group study of 60 patients with obstructive lung disease was performed to assess tachyphylaxis with inhaled atropine sulfate versus placebo. Forty patients completed the study; twenty-one were treated with placebo and nineteen were treated with atropine sulfate. Atropine and placebo groups were compared before and after inhaled atropine by spirometry at Weeks zero, 6, and 14. Medication side effects, other medication usage, and symptoms were recorded daily. Comparison of FEV1 response to atropine sulfate from baseline at Weeks zero, 6, and 14 did not show a statistically significant decrease. Inhaled atropine sulfate continued to be an effective bronchodilator in both placebo groups and atropine sulfate groups. There was no evidence of significant tachyphylaxis with atropine. Significant side effects in the atropine group when compared with placebo included dry mouth, dry skin, rapid heart rate, and nausea.

Transdermal scopolamine attenuates methacholine-induced bronchospasm.

Anticholinergic agents have been widely used in the management of asthma. The use of scopolamine has been limited by significant side effects. Transdermal delivery of scopolamine (TS) has, however, been used successfully for the prevention of motion sickness. The purpose of this study was to determine if TS would decrease methacholine-induced bronchospasm in a group of subjects with mild asthma. Bronchoprovocational challenges with inhaled methacholine were performed on three separate occasions in 10 male subjects who each had a past history of asthma. After a baseline challenge, each subject received, in a double-blinded fashion, either a placebo patch or TS patch. The challenge was then repeated after at least 36 hours, and the alternate patch was then dispensed. The provocative dose producing a fall in FEV1 by 20% from baseline was then calculated by linear regression analysis. No significant change in baseline pulmonary function was noted with placebo patch or TS. With the use of TS, there was a small but significant increase in the provocative dose producing a fall in FEV1 by 20% from baseline for the group (p less than 0.05). In conclusion, we were able to demonstrate that a TS patch worn for a short period of time, can significantly decrease airway reactivity to methacholine in some patients with hyperactive airways.

A comparison of the effect of ipratropium and albuterol in the treatment of chronic obstructive airway disease.

Twenty-five subjects with moderate to severe chronic obstructive airway disease were studied to compare the effect of ipratropium bromide, albuterol, and placebo on the forced expiratory volume in 1 s, (FEV1), forced vital capacity, heart rate, and blood pressure during six hours. Ipratropium produced a significantly greater improvement than albuterol in the FEV1 at 30 minutes and at 3, 4, and 5 hours and in the forced vital capacity at one through six hours. Fifteen subjects did not demonstrate a 15% improvement and at least a 200-mL increase in the FEV1, 15 minutes after metaproterenol sulfate aerosol. All 15 did improve after ipratropium therapy during the study. Ipratropium was effective significantly longer than albuterol. Subjects with better peak responses to ipratropium had a lower FEV1 percent predicted and a greater pack-year smoking history. In patients with chronic obstructive airway disease, ipratropium produces a longer duration of action than albuterol. It is more effective than albuterol in treating severely obstructed individuals and those not responding to metaproterenol. It is equally effective in treating others.

Intermittent negative pressure ventilation in the treatment of respiratory failure in progressive neuromuscular disease.

Five men with degenerative neuromuscular diseases (three with amyotrophic lateral sclerosis [ALS] and two with Duchenne's muscular dystrophy [DMD]) who had respiratory failure were treated with intermittent negative pressure ventilation (NPV). One patient with ALS in severe acute respiratory failure was successfully treated with NPV alone. This patient and two other ALS patients in chronic respiratory failure with PaCO2 elevation stabilized or improved their vital capacity (VC) and lowered their PaCO2 after 5 to 11 weeks of therapy. Finally, intermittent NPV was used to replace 24-hour positive pressure ventilation in two patients with DMD. It is concluded that intermittent NPV may stabilize or temporarily improve the respiratory status in patients with progressive neuromuscular diseases.

Respiratory system in amyotrophic lateral sclerosis.

Failure of the respiratory system is the most common cause of death in amyotrophic lateral sclerosis. This is due to weakened respiratory musculature resulting in respiratory failure, ineffective cough, and failure to protect the lungs from aspiration. Treatment is only supportive at present, but mechanical ventilation with either negative or positive pressure offer some life-extending possibilities. The respiratory system should be closely monitored as early identification of problems may allow better insight into the immediate prognosis.

Severe hypoxemia in farmer's lung disease with normal findings on chest roentgenogram.

A 33-year-old woman farmer developed an acute episode of fever, cough, and shaking chills with persistent shortness of breath. Her PaO2 was 51 with a restrictive pattern on pulmonary function. Her diffusion capacity was 36 percent of predicted. In spite of these abnormalities, she always had normal chest roentgenographic findings. Further studies, including a lung biopsy, led to the diagnosis of farmer's lung disease.

Pulmonary inflammation in autoimmune MRL/Mp-lpr/lpr mice. Histopathology and bronchoalveolar lavage evaluation.

Early detection of lupus pneumonitis is difficult because it requires lung biopsy. The authors describe here in detail the age-related histologic changes in pulmonary inflammation, the age-related changes in bronchoalveolar lavage (BAL), and the effect of cyclophosphamide (8 mg/kg) on pulmonary inflammation and bronchoalveolar lavage in MRL/Mp-lpr/lpr mouse, an animal model of systemic lupus erythematosus. To assess the evolution of pulmonary inflammation and response to cyclophosphamide therapy, they compared the age-related progression of pulmonary inflammation with sequential changes in BAL cell populations in this autoimmune mouse model. A striking similarity was noted between age-related changes in pulmonary inflammation and lymphocyte counts in BAL. A trend to reduction in histologic evidence of inflammation was reflected by lymphocytes in BAL in cyclophosphamide-treated (8 mg/kg/day) males but not in females. There was a striking sex-related difference in that the histologic evidence of pulmonary inflammation and bronchoalveolar lavage lymphocyte count in cyclophosphamide-treated males was significantly lower than cyclophosphamide-treated females of the same age.

Dietary evaluation of outpatients with chronic obstructive pulmonary disease.

Protein-calorie malnutrition is prevalent among individuals with chronic obstructive pulmonary disease (COPD), and suboptimal body weight has been associated with increased morbidity and mortality. Pulmonary function, anthropometric measurements, and dietary intake were evaluated in 64 outpatients with stable COPD to assess interrelationships of those parameters. Those individuals with body weights less than 75% of standard for height, age, and sex had the greatest degree of airway obstruction, poorest lung diffusing capacity, and greatest loss of body fat and muscle mass. Contrary to what had been anticipated, calorie and protein intake levels were highest in the less than 75% of standard body weight group, decreased as relative body weight increased, and were lowest in the greater than 105% of standard body weight group. Those results indicate that caloric needs increase as COPD progresses. Intake levels of calcium, phosphorus, iron, vitamin A, thiamin, riboflavin, niacin, and vitamin C were adequate in terms of the RDAs and were not related to relative body weight.

Role of corticosteroids in the development of pneumonia in mechanically ventilated head-trauma victims.

The development of pneumonia was monitored in head-trauma patients requiring mechanical ventilation. Of the 66 patients studied, 15 (23%) developed pneumonia within 14 days after ICU admission. In each case the diagnosis was based on x-ray evidence and at least two of the following: increased white blood cell count, increased fever, and/or increased sputum production with a predominant organism on the sputum stain. Coagulase-positive Staphylococcus aureus was the most common etiologic agent. There was no difference in the occurrence of pneumonia between patients treated with no steroids or with low, moderate, or high steroid doses. Although there was an association between thiopental use and the development of pneumonia, dexamethasone treatment was not a significant risk factor in the development of pneumonia in this patient population.

The prevalence and determinants of nutritional changes in chronic obstructive pulmonary disease.

Sixty outpatients with chronic obstructive pulmonary disease underwent nutritional, physiologic, and psychologic evaluation to determine the prevalence of nutritional depletion and the relationship to physiologic and psychologic factors. Weight loss was reported in 27 percent. Triceps skinfolds (TSF) were less than 60 percent of standard in 33 percent, none had mid-arm muscle circumference (MAMC) less than 60 percent of standard, and 5 percent had body weight (BW) less than 60 percent of ideal. Values for BW-percent of ideal, TSF-percent of standard, and MAMC-percent of standard were inversely correlated with the percent of estimated caloric expenditure ingested. Also, BW percent was correlated with FEV1 percent predicted, diffusion capacity percent predicted, and oxygen consumption/kg at rest (VO2 percent/kg). There were five variables that explained 62.6 percent of the variation in BW percent: VO2/kg at rest explained 22.2 percent; ventilatory equivalent 13.5 percent; PaCO2 9.8 percent; log vital capacity percent predicted 9.2 percent; and depression 7.8 percent. It is concluded that increased caloric utilization without adequate compensation in dietary intake is the reason for nutritional depletion.