Characteristics of patients with seasonal allergic rhinitis and concomitant asthma.

BACKGROUND: Allergic rhinitis and asthma often co-exist and appear to produce a continuum of airway disease, but whether the clinical characteristics of asthma in patients with seasonal rhinitis differ from those of persistent asthma has not been examined. OBJECTIVE: The aim of this retrospective study was to characterize the clinical features of patients with seasonal allergic rhinitis with concomitant asthma and to compare them with those in patients with persistent asthma. METHODS: The patient populations for this study were derived from nine prospective, placebo-controlled planned clinical trials of similar design. Six studies (958 patients) enrolled patients with seasonal allergic rhinitis and concomitant asthma; three (607 patients) involved patients with persistent asthma. In all studies, patients were excluded from oral corticosteroid therapy in the preceding 3 months, and from inhaled corticosteroids in the preceding month. RESULTS: Patients with seasonal rhinitis and asthma had a significantly (P<0.001) higher total asthma symptom score than those with persistent asthma. In particular, cough was three times more severe. The need for beta(2)-agonist as a rescue medication and the ratio of forced expiratory volume in 1 s/forced vital capacity (FVC) were similar in the two groups whereas forced expiratory fraction 25-75%/FVC was significantly (P<0.02) reduced in the persistent asthmatics. Asthma and nasal symptom severity scores were correlated in patients with seasonal rhinitis and asthma (P<0.0001). CONCLUSIONS: Patients with seasonal allergic rhinitis and concomitant asthma appear to differ from those with persistent asthma. A prospective study should be designed to discover whether patients with seasonal rhinitis and asthma may represent a distinct nosological entity, 'allergic airway disease'.

Comparison of once-daily to twice-daily treatment with mometasone furoate dry powder inhaler.

BACKGROUND: Once-daily dosing with an effective inhaled corticosteroid (ICS) would likely enhance compliance and, therefore, aid in the management of asthma. OBJECTIVE: Several once-daily dosing regimens of mometasone furoate (MF) administered by dry powder inhaler (DPI) were compared with a twice-daily dosing regimen in 286 patients with mild to moderate persistent asthma who were previously being treated with ICS. METHODS: During a 2-week open-label phase, patients received MF-DPI, 200 microg twice daily. They were then randomized to continue MF-DPI, 200 microg twice-daily treatment or to receive MF-DPI, 200 microg once daily in the morning (AM), 200 microg once daily in the evening (PM), 400 microg once daily AM, or placebo as part of the 12-week, double-blind phase. The primary efficacy variable was the mean change from the baseline to endpoint (last evaluable observation) for FEV1. RESULTS: Once-daily MF-DPI, 400 microg, AM maintained FEV1, and morning peak expiratory flow rate, FVC, FEF25%-75%, and asthma symptom scores, at levels similar to those for MF-DPI, 200 microg twice daily and significantly better than placebo. Once-daily MF-DPI, 200 microg, PM was effective in maintaining pulmonary function, but was less effective on other efficacy measures. In comparison to the other MF-DPI groups, once-daily MF-DPI, 200 microg, AM was not as effective overall. The incidence of local adverse events, including oral candidiasis, was low with all dosages. CONCLUSIONS: Once-daily MF-DPI, 400 microg, AM was as effective as MF-DPI, 200 microg twice daily, whereas once-daily MF-DPI, 200 microg, was more effective when administered in the evening compared with morning, for patients receiving ICS therapy. Once-daily dosing offers an effective and convenient treatment that could aid compliance in the treatment of asthma.

Inhaled mometasone furoate reduces oral prednisone requirements while improving respiratory function and health-related quality of life in patients with severe persistent asthma.

BACKGROUND: Inhaled corticosteroid therapy in severe persistent asthma has been shown to reduce or eliminate oral corticosteroid (OCS) use while retaining effective asthma control. OBJECTIVE: We sought to evaluate the ability of mometasone furoate (MF) delivered by means of dry powder inhaler to reduce daily oral prednisone requirements in OCS-dependent patients with severe persistent asthma. METHODS: We performed a 12-week, double-blind, placebocontrolled trial (21 centers, 132 patients) comparing 2 doses of MF (400 and 800 microg administered twice daily) with placebo, followed by a 9-month open-label phase in which 128 patients received treatment with MF. RESULTS: At the endpoint of the double-blind trial, MF 400 and 800 mg twice daily reduced daily OCS requirements by 46.0% and 23.9%, respectively, whereas placebo increased OCS requirements by 164.4% (P <.01). Oral steroids were eliminated in 40%, 37%, and 0% of patients in the MF 400 and 800 mg twice daily and placebo groups, respectively. Pulmonary function and quality of life significantly increased for MF-treated patients. Further reductions in OCS requirements were achieved with long-term MF treatment in the open-label phase. CONCLUSION: MF inhaled orally as a dry powder is an effective alternative to systemic corticosteroids in patients with severe persistent asthma.

An easy-to-use dry-powder inhaler.

The mometasone furoate dry-powder inhaler is a novel device designed to support compliance by delivering a topical corticosteroid in a simple three-step operation. This breath-actuated inhaler uses a stabilized agglomerate formulation to measure and deliver accurate, uniform, and precise doses of drug over a range of inspiratory flow rates. Laboratory and clinical data have shown that the design produced a simple, clinically effective inhaler for the treatment of adults and children 12 years of age and older with mild, moderate, or severe persistent asthma.

The effect of adding ipratropium bromide to salbutamol in the treatment of acute asthma: a pooled analysis of three trials.

OBJECTIVE: To assess the effect on FEV1 and clinical outcomes of adding ipratropium bromide to salbutamol in the treatment of acute asthma. METHODS: We conducted a pooled analysis of three randomized double-blinded clinical trials conducted in the United States, Canada, and New Zealand. The studies enrolled 1,064 patients aged 18 to 55 years who presented at the emergency department with acute asthma. Patients were randomized to treatment with a combination of nebulized 2.5 mg salbutamol plus 0.5 mg ipratropium bromide, or 2.5 mg salbutamol alone. Medications were administered at baseline and, in the US study, at 45 min. FEV1 was measured at baseline, 45 min, and 90 min. Patients were followed up for 48 h after hospital discharge for occurrence of asthma exacerbation and hospitalization. RESULTS: Treatment groups were comparable at baseline. Of the 1,064 patients randomized, 1,015 patients (95%) remained in the study for measurement at 45 min, and 961 patients (90%) completed the final measurement at 90 min. Comparison of overall improvement in FEV1 at 45 min indicated a better response for patients receiving combination therapy (mean difference=43 mL, 95% confidence interval [CI]=-20, 107). The distribution of change in FEV1 was skewed by a small number of patients with extreme values (38 of 1,064=3.6%) that may have been due to unreliable lung function testing. Removing these outliers produced a larger and more precise estimate of effect (mean difference=55 mL, 95% CI=2,107). Because the distribution was skewed, we performed nonparametric analyses that showed evidence of a beneficial effect of combination therapy. The difference between median values at 45 min is 40 mL (Wilcoxon p value=0.03). In addition, 4.9% (95% CI=-1%, 11%) more patients in the combination group achieved at least 20% of their potential improvement, as measured by the difference between their baseline FEV1 and their predicted FEV1. Patients receiving combination therapy had lower risk for each of three clinical outcomes: the need for additional treatment (relative risk [RR]=0.92, 95% CI=0.84, 1.0), risk of asthma exacerbation (RR=0.84, 95% CI=0.67, 1.04), and risk of hospitalization (RR=0.80, 95% CI=0.61, 1.06). CONCLUSION: Adding ipratropium bromide to salbutamol in the treatment of acute asthma produces a small improvement in lung function, and reduces the risk of the need for additional treatment, subsequent asthma exacerbations, and hospitalizations. These apparent benefits of adding ipratropium bromide were independent of the amount of beta-agonist that had been used earlier in the attack, and possibly related to a recent upper respiratory tract infection. Confirmatory studies are needed, especially for clinical outcomes.

Emergency treatment of acute asthma with albuterol metered-dose inhaler plus holding chamber: how often should treatments be administered?

STUDY OBJECTIVE: To determine the optimal treatment interval for administering albuterol metered-dose inhaler (MDI) with a holding chamber to patients presenting to the emergency department (ED) with acute asthma. DESIGN: Prospective, randomized, double-blind study. SETTING: EDs of two affiliated teaching hospitals in the Bronx, NY. PATIENTS: One hundred adult patients with acute asthma and FEV1 <60% predicted of normal. INTERVENTIONS: At entry (T=0 min), eligible patients all openly received inhaled albuterol (six puffs) via MDI with a spacer. Subsequently, in a double-blind fashion, they received six puffs of albuterol or placebo with new MDIs and spacers at 30, 60, and 90 min such that group 1 (n=34) received albuterol every 30 min, group 2 (n=33) every 60 min, and group 3 (n=33) at 120 min only. FEV1 and vital signs were measured at T=0 and at 15, 30, 60, 90, and 120 min following initial treatment. Potassium levels were measured at T=0 and 120 min. Adverse events, the use of additional inhaled beta-agonists or systemic corticosteroids, and hospitalization rates were recorded. MEASUREMENTS AND RESULTS: At T=0, the groups did not differ in age, FEV1, or prescribed asthma medications. All groups showed significant improvement in FEV1 (p<0.05; T=120 vs 0 min). The conditions of groups 1 and 2 improved significantly more than those of group 3, but did not differ compared to each other. The mean+/-SEM change in FEV1 (T=120 vs 0 min) was 0.993+/-0.108, 0.858+/-0.135, and 0.321+/-0.056 L, respectively, for the three groups. Separate analysis for patients with FEV1% <40% or >40% predicted showed similar results. However, patients who initially were low responders to albuterol treatment (<15 percentage point increase at 15 min) improved significantly with 30-min treatments compared to the other two treatment regimens. Patients who initially responded with >15 percentage point increase in FEV1 at 15 min following initial albuterol inhalation benefited equally from 30- or 60-min treatments compared to 120 min. Potassium levels did not change significantly during the study. Adverse events and hospitalization rates were equivalent. After the conclusion of the study, group 3 patients required a greater number of beta-agonist treatments prior to eventual discharge from the ED. CONCLUSIONS: For acute asthma, albuterol MDI with a holding chamber can be given optimally at 60-min intervals with minimal adverse effects for the majority of patients. However, patients who initially demonstrate a low or poor bronchodilator response to albuterol should be given subsequent treatments at 30-min intervals. This will optimize care and conserve resources for patients who will benefit the most.

A comparison of ipratropium and albuterol vs albuterol alone for the treatment of acute asthma.

To evaluate the role of inhaled ipratropium bromide in acute asthma, a double-blind study of 384 emergency department patients compared the effect of the combination of ipratropium and albuterol with that of albuterol alone. Patients were randomized to receive nebulizer treatments with either 2.5 mg of albuterol or 2.5 mg of albuterol mixed with 0.5 mg of ipratropium bromide at entry and at 45 min. Spirometry, vital signs, and oxygen saturation were measured before and at 45 and 90 min following the nebulizer treatments. Serum potassium levels were obtained at entry and 90 min. The two groups did not differ significantly in age (mean +/- SD = 33.4 +/- 9.3 and 32.5 +/- 9.7 years for the albuterol and ipratropium group and the albuterol group, respectively), baseline FEV1 (mean +/- SD = 1.22 +/- 0.42 and 1.25 +/- 0.44 L respectively), or prior use of asthma medications. At 45 min, there were significantly more responders (15% increase in FEV1 over baseline) in the group receiving albuterol and ipratropium compared with albuterol and saline solution (85% and 78%, respectively; p = 0.045), but the median change in FEV1 from baseline did not differ (0.530 L for the albuterol and ipratropium group and 0.420 L for the albuterol and saline solution group; p = 0.347). By 90 min, the percentage of responders did not differ (88% and 89%, respectively), and the median change in FEV1 was 0.680 L for the group receiving albuterol and ipratropium and 0.650 L for the group receiving albuterol and saline solution (p = 0.693). There were no significant adverse events experienced by patients in either group. Furthermore, there were no significant differences in the number of patients requiring additional therapy in the emergency department or hospitalization. We conclude that in this population of inner city asthmatics, we were unable to demonstrate significant additive benefit of nebulized ipratropium bromide to nebulized albuterol.

Upper airway obstruction in a woman with AIDS-related laryngeal Kaposi's sarcoma.

Kaposi's sarcoma rarely causes upper airway obstruction. In the only two previously reported cases, both patients were men who died of hemorrhage shortly after tracheostomy. We describe a 45-year-old woman with AIDS who presented with stridor secondary to Kaposi's sarcoma of the larynx. To our knowledge, this is the first report of this presentation in a woman and the first reported patient with Kaposi's sarcoma to survive tracheostomy.

Inhaled furosemide is not effective in acute asthma.

As previous studies have suggested that inhaled furosemide may have a protective effect against certain types of provocative challenges in asthmatic subjects, we investigated the role of furosemide in treating acute asthma exacerbations. Twenty-four patients (n = 24) with acute asthma were entered into the study on presenting to the emergency department. They were blindly randomized to receive one of three drug regimens: (1) inhaled furosemide (40 mg) (n = 8); (2) inhaled metaproterenol (15 mg) (n = 7); or (3) the combination of furosemide (40 mg) and metaproterenol (15 mg) (n = 9). We measured FEV1 at entry (time 0) and 15, 30, 45, and 60 min after inhalation of the individual drugs or the combination from a face mask nebulizer. At entry, the three groups did not differ significantly in age (mean +/- SEM = 37.6 +/- 3.6, 38.5 +/- 3.6, and 41.0 years, respectively; p = 0.770), baseline FEV1 (1.01 +/- 0.27, 1.04 +/- 0.27, and 1.25 +/- 0.14 L, respectively; p = 0.620), or theophylline levels (2.87 +/- 1.8, 7.39 +/- 2.8, and 5.29 +/- 2.6 micrograms/ml, respectively; p = 0.498). Pretreatment and posttreatment potassium levels were similar among the three groups. Inhalation of furosemide alone resulted in a 14.9 +/- 10.5 percent change in FEV1 percent from baseline, which was not statistically significant. In contrast, metaproterenol alone resulted in a 42.9 +/- 15.2 percent increase in FEV1 percent (F ratio = 6.226; p = 0.0028). The combination of furosemide and metaproterenol resulted in a change in FEV1 percent that was not statistically different compared with metaproterenol alone (FEV1 percent = 41.9 +/- 12 percent). No significant adverse effects occurred in any of the groups.

A comparison of inhaled ipratropium, oral theophylline plus inhaled beta-agonist, and the combination of all three in patients with COPD.

To evaluate the role of inhaled ipratropium bromide alone vs oral theophylline plus inhaled beta-agonist or the combination of all three in patients with stable COPD, the following double-blind, placebo-controlled study was conducted. Forty-eight patients with stable COPD (mean age, 61.8 years, with mean baseline FEV1 < 1.0 L) were randomized on four separate days to receive the following drug regimens: (1) theophylline tablets (dose previously determined to result in blood level of 12 to 18 mg/L), followed by inhaled albuterol (2 puffs via metered-dose inhaler [MDI]), followed by inhaled placebo (2 puffs via MDI); (2) oral placebo followed by ipratropium (2 puffs via MDI; 36 micrograms), followed by inhaled placebo; (3) oral theophylline, followed by albuterol, followed by ipratropium; or (4) oral placebo followed by two inhaled placebos. On study days, spirometry and heart rate were measured at time 0, 30 min, 60 min, and hourly for 6 h. The FEV1 peak change (liters) and area under the curve (liter x hours) for the treatment groups were compared. Ipratropium was more effective than placebo (p = 0.001 and p = 0.0078, respectively). The combination of albuterol and theophylline was superior to ipratropium alone (p = 0.001 and p = 0.0001, respectively), and all three drugs together were superior to the combination of albuterol and theophylline (p = 0.0373 and p = 0.0289), respectively; one-sided test of hypotheses). Peak heart rates were significantly higher for treatment groups compared with placebo groups (p = 0.0001). However, theophylline and albuterol and the combination of all three drugs resulted in greater peak heart rates than did ipratropium alone (p = 0.001). These data suggest that for patients with stable COPD, combination therapy with ipratropium (two puffs), theophylline, and albuterol (two puffs) is superior to ipratropium alone or the combination of theophylline and albuterol.

Lung cancer in patients with immunodeficiency syndrome.

We report adenocarcinoma of the lung in seven patients with human immunodeficiency virus (HIV) infection. We compared age, clinical findings and survival data with a sex-matched control group of HIV-negative patients with adenocarcinoma of the lung. Median age of HIV-infected patients with lung cancer was lower than in control patients with lung cancer. The HIV-infected patients had more systemic symptoms and abnormal physical findings than control subjects. Both groups had smoking histories. Laboratory data were similar but control subjects had lower blood oxygen tensions than did HIV patients; HIV patients had more abnormalities on chest roentgenograms and computed tomography scans than did control subjects. All HIV-infected patients were stage IV. Median survival was 4 weeks. For control patients, 50 percent had stage IV disease; median survival was 25.5 weeks. Thus, patients with HIV infection develop lung cancer at a younger age than sex-matched control subjects and undergo a more fulminant course with shortened survivals.

Respiratory syncytial virus infection in an adult with Wegener's granulomatosis.

Respiratory syncytial virus (RSV) has been documented as a pathogen in adults who are immunocompromised because of various underlying conditions. To our knowledge, this is the first report of a patient with Wegener's granulomatosis (WG) and RSV infection resulting in a fatal outcome.

Bronchodilator responses to anticholinergic and beta-adrenergic agents in acute and stable COPD.

Patients with COPD may respond differently to anticholinergic and beta-agonist bronchodilators. Previously, in acutely ill COPD patients, we showed similar improvements in pulmonary function after each drug (study 1). The responses of the same patients when stable are now reported (study 2). Patients received ipratropium bromide (54 micrograms) (n = 16) or metaproterenol sulfate (1.95 mg) (n = 14) via an MDI attached to a delivery device as in study 1. Ninety minutes after the first medication, patients received the second. Spirometry was measured at entry and at 30-min intervals following the first drug and at the same times after the second drug. Results were as follow: The groups did not differ in clinical characteristics. However, for both groups, there was significantly less airway obstruction at entry into study 2. In study 1, ipratropium resulted in significant improvement in FEV1 (0.62 +/- .08 to 0.88 +/- .11 L; mean increase 24 percent; p less than 0.05) with no further change after crossover. In study 2, ipratropium produced similar improvements in FEV1 by 90 minutes (0.94 +/- .09 to 1.3 +/- .09 L; mean increase 25 percent; p less than 0.05), with no further improvement after crossover. For metaproterenol, in study 1, the improvement in FEV1 was not significantly different than that for ipratropium (FEV1; 0.71 +/- .07 to 0.92 +/- 0.06 L; mean increase 18 percent; p less than 0.05), with no further improvement after crossover. In study 2, improvement with metaproterenol was significant and similar to study 1 (FEV1: 0.96 +/- .06 to 1.21 +/- .09 L; mean increase 18 percent; p less than 0.05). Thus, ipratropium and metaproterenol similarly improved pulmonary function in COPD patients when stable and during acute exacerbations.

Natural killer cell activity in a rat model of amiodarone-induced interstitial lung disease.

The role of lymphocytes in the pathogenesis of amiodarone-induced lung disease is controversial. Increases in the percentages of lymphocytes in bronchoalveolar fluid of both patients and animals with amiodarone pulmonary toxicity have been reported. To assess whether these lymphocytes are functionally activated, we measured natural killer cell activity in the lungs and blood of rats with amiodarone-induced pulmonary toxicity. Amiodarone treated rats exhibited pathologic evidence of amiodarone-induced lung disease after one week of treatment and this injury was sustained and more extensive during the remainder of the study period. Control rats had histologically normal lungs. Blood NK activity was equally present in both amiodarone-treated and control groups and was not significantly different over the course of the study (16 +/- 3 percent and 13 +/- 2 percent, respectively; p greater than 0.05). Thus, NK cells were activated only in the lungs of rats treated with amiodarone, suggesting a local immune response in the lung. These data support the concept that lymphocytes play an important role in the pathogenesis of amiodarone-induced lung disease.

Anticholinergic bronchodilators in obstructive airway disease.

The appropriate use of anticholinergic bronchodilating agents in the management of patients with chronic obstructive pulmonary disease (COPD) or asthma is the subject of renewed academic interest. This article examines the physiology of airway function and the pharmacology of anticholinergic agents, and reviews the relevant clinical literature concerning the use of these agents for individuals with chronic obstructive pulmonary disease or asthma. It is suggested that anticholinergic bronchodilators are safe and effective as first-line therapy for COPD and should be considered as adjunctive therapy for asthma.

Inspiratory flow dynamics during mechanical ventilation in patients with respiratory failure.

We studied the effect of inspiratory flow rate on respiratory resistance during mechanical ventilation in 15 patients with acute respiratory failure (ARF). Resistance was measured by both constant flow inflation and occlusion methods as inspiratory flow rates were increased from 0.66 to 2.0 L/s. Endotracheal tube resistance was subtracted from total resistance to obtain respiratory resistance. In contrast to the flow-dependent increase in endotracheal tube resistance, respiratory resistance decreased continuously as flow rate and airway pressure increased, except in four of six patients with asthma in whom respiratory resistance increased as flow increased. Mechanical airway dilatation, tissue resistance, stress relaxation, and time-constant inequalities may contribute to the decrease in respiratory resistance. In status asthmaticus, however, the effects of turbulence, noncompliant airways, and/or "reflex" bronchoconstriction may be sufficient to cause a flow-dependent increase in resistance.

A comparison of the effects of ipratropium bromide and metaproterenol sulfate in acute exacerbations of COPD.

Thirty-two patients presenting with acute exacerbations of chronic obstructive pulmonary disease were entered into the following double-blind, crossover study. First (time 0), patients inhaled either ipratropium bromide (54 micrograms) or metaproterenol sulfate (1.95 mg) via a metered dose inhaler (MDI) attached to a device (Inspirease) (phase 1). After 90 minutes, they inhaled whichever of the two medications they had not received in phase 1. This is referred to as phase 2. Pulmonary function (FEV1 and FVC) was measured at time 0, and at 30, 60, and 90 minutes following phase 1 treatment, and at 30, 60, and 90 minutes following phase 2 treatment (120, 150, and 180 minutes from the start of the study). Arterial blood gas samples (n = 20) were obtained at entry into the study and 30 and 90 minutes after phase 1 medication. The groups did not differ in age, degree of airway obstruction, hypoxemia, or theophylline usage at the start of the study. In phase 1, at 90 minutes, pulmonary function in both groups significantly and similarly improved. For ipratropium, FEV1 improved from 0.62 +/- 0.08 L to 0.88 +/- 0.11 L (p less than 0.01) and for metaproterenol FEV1 improved from 0.69 +/- 0.06 to 0.92 +/- 0.09 L (p less than 0.01). There was no further improvement with phase 2 treatment for either group. Thirty minutes after inhaling ipratropium, there was a small but significant rise in PO2 (5.8 +/- 3.0 mm Hg; p less than 0.05) while metaproterenol inhalation resulted in a 6.2 +/- 1.2 mm Hg decline in PO2 (p less than 0.05). These changes were not sustained at 90 minutes. We concluded that for acute exacerbations of COPD, both ipratropium and metaproterenol are effective medications when administered via an MDI attached to a device (Inspirease). However, ipratropium may be a safer choice as it initially did not cause a decline in blood oxygenation.

Maximal inspiratory pressure is not a reliable test of inspiratory muscle strength in mechanically ventilated patients.

Maximal Inspiratory pressure (MIP) is an important clinical method used to assess respiratory muscle strength. The reliability and reproducibility of this measurement in mechanically ventilated patients is not certain. In 14 stable, mechanically ventilated patients, capable of spontaneous inspiratory efforts, we assessed maximal inspiratory efforts using the technique originally described by Marini and associates. MIP was measured in triplicate, by one to five experienced investigators, on one to seven successive days, for a total of 396 determinations on 54 patient days. The coefficients of variation among the triplicate efforts averaged 12 +/- 1%, indicating the test to be highly reproducible. There was significant variation among the MIP reported by different investigators studying the same patient on the same day (32 +/- 4%). The differences between best MIP by different investigators averaged 12.6 +/- 1.3cm H2O (40 +/- 4%). In 17 of 44 cases, one investigator placed MIP above -30cm H2O, whereas another placed it below. ANOVA showed that MIP was significantly affected by investigator (p less than 0.0001) as well as by patient (p less than 0.0001). Because "true" MIP must be equal to or greater than the best measured MIP, these data indicate that the MIP is commonly underestimated in patients receiving mechanical ventilation, even when standardized technique is used. Furthermore, our data show that reproducibility of triplicate MIP determination by a single observer does not indicate that the test is reliable.

Adaptations in the diaphragm's in vitro force-length relationship in patients on continuous ambulatory peritoneal dialysis.

In patients on continuous ambulatory peritoneal dialysis (CAPD) for more than 6 wk, we measured functional residual capacity (FRC), maximum inspiratory and transdiaphragmatic pressure, diaphragm length, and radius of curvature (roentgenographic methods) as functions of the volume of peritoneal dialysate (PD) instilled within the abdominal cavity. This allowed in vivo characterization of the human diaphragm's force-length relationship. As PD volume increased from zero to 3 L, FRC decreased from 2.41 +/- 0.29 L to 1.93 +/- 0.072 L; mean total diaphragm length index (TDLI) increased from 0.22 +/- 0.01 to 0.28 +/- 0.01, and diaphragm radius of curvature remained unchanged. Respiratory muscle strength increased as a function of dialysate volume, reaching its maximum after the infusion of 3 L PD. In contrast, normal subjects achieved maximal inspiratory muscle force at their normal FRC, with a mean TDLI of 0.26 +/- 0.01 and showed no further increase as the diaphragm lengthened. We conclude that the human diaphragm may be capable of an adaptive rightward shift in its force-length relationship when it is chronically lengthened by CAPD.