Associations Between Religious/Spiritual Coping and Depression Among Adults with Cystic Fibrosis: A 12-Month Longitudinal Study.

Individuals with cystic fibrosis (CF) face a challenging disease, and depression is a significant concern. Many patients draw on religious/spiritual resources to assist them in managing the demands of chronic illness; however, these coping efforts rarely have been evaluated among adults with CF. This longitudinal study examined relationships between distinct types of positive and negative religious/spiritual coping at baseline (assessed with the RCOPE) and depression screening outcomes 12 month later (assessed with the Hospital Anxiety and Depression Scale). In logistic regression analyses controlling for disease severity (FEV1% predicted), lower likelihood of depression caseness at 12 months was predicted by higher general religiousness at baseline, greater use of benevolent religious reappraisal coping, greater use of spiritual connection coping, and lower spiritual discontent. Results suggest that distinct aspects religious/spiritual coping have differential associations with subsequent depression outcomes. Findings extend prior research to an important, understudied medical population, and address a clinically meaningful outcome.

Longitudinal associations between gratitude and depression 1 year later among adult cystic fibrosis patients.

Individuals with cystic fibrosis (CF) are confronted by a range of difficult physical and psychosocial sequelae. Gratitude has drawn growing attention as a psychosocial resource, but it has yet to be examined among adults with CF. The current investigation evaluated longitudinal associations between trait gratitude and subsequent outcomes from depression screening 12 months later, adjusting for disease severity (FEV1% predicted) and other significant clinical or demographic covariates. Participants were 69 adult CF patients recruited from a regional adult treatment center. They completed a validated measure of gratitude (Gratitude Questionnaire-6) at baseline and a screening measure of depression (Hospital Anxiety and Depression Scale) at 12-month follow-up. In a logistic regression analysis controlling for disease severity, higher levels of baseline gratitude were associated with reduced likelihood of depression caseness at 12 months (OR .83, 95% CI .73-.91, p = .001). Gratitude remained predictive after adjusting for other psychosocial resource variables (i.e., perceived social support and positive reframing coping). Findings offer an initial indication of the potential salutary role of dispositional gratitude in an understudied clinical population.

Lubiprostone for constipation in adults with cystic fibrosis: a pilot study.

BACKGROUND: Constipation is prevalent in the cystic fibrosis (CF) population and yet there are few data demonstrating the effectiveness of currently used treatments. Lubiprostone is a laxative that works by activating the type 2 chloride channel in the gastrointestinal tract and thus has the potential to be especially effective for constipation associated with CF. OBJECTIVE: To evaluate the effectiveness of lubiprostone for the treatment of constipation in adults with CF. METHODS: In this pilot study, participants acted as their own controls and comparisons were made between run-in and treatment periods. During the 2-week run-in period, participants continued their usual treatment for constipation; during the 4-week treatment period, participants received lubiprostone 24 µg twice daily. Efficacy outcomes included spontaneous bowel movement frequency, Bristol Stool Scale scores, and Patient Assessment of Constipation Symptoms (PAC-SYM) survey scores. Outcomes were assessed during both the run-in and treatment periods (0, 2, and 4 weeks of treatment). Safety outcomes included spirometry, body weight, and serum chemistry. RESULTS: Seven participants completed the study. Mean (SD) baseline forced expiratory volume in 1 second was 83.0% (9.4) of predicted and body mass index was 24.0 (2.8) kg/m², indicating an overall healthy, well-nourished group of adults with CF. Lubiprostone improved overall symptoms of constipation as measured by PAC-SYM survey scores (1.18 [0.56], 0.54 [0.27], and 0.44 [0.36] at 0, 2, and 4 weeks, respectively; p < 0.001). Spontaneous bowel movement frequency and Bristol Stool Scale scores were not statistically significantly different between periods. There were no differences in safety measures. Transient chest tightness and shortness of breath were reported by 2 separate participants, although neither participant withdrew due to these adverse effects. CONCLUSIONS: Lubiprostone may be an effective option for the treatment of constipation in adults with CF.

Use of the chloride channel activator lubiprostone for constipation in adults with cystic fibrosis: a case series.

OBJECTIVE: To describe the use of lubiprostone for constipation in 3 adults with cystic fibrosis (CF). CASE SUMMARY: This case series describes the use of lubiprostone for the treatment of constipation in 3 adults with CF (mean +/- SD length of therapy 17.3 +/- 1.5 mo). All 3 patients were prescribed lubiprostone 24 microg twice daily after hospitalization for treatment of intestinal obstruction. Patient 1 continues on chronic polyethylene glycol (PEG) 3350 and lubiprostone and has not had a recurrence of obstruction. Patient 2 requires aggressive chronic therapy with PEG 3350, lubiprostone, and methylnaltrexone. She has had 1 recurrence of obstruction. Patient 3 continues with lubiprostone taken several times per week with good control of constipation and no recurrence of obstruction to date. The adverse effect profile has been tolerable in all 3 patients. DISCUSSION: CF is caused by a genetic mutation resulting in a dysfunctional or absent CF transmembrane conductance regulator that normally functions as a chloride channel. This results in viscous secretions in multiple organ systems including the lungs and intestinal tract. Accumulation of viscous intestinal contents contributes to constipation, which is common among adults with CF and can sometimes lead to intestinal obstruction. Lubiprostone is indicated for chronic constipation and works by activating type 2 chloride channels (ClC-2) in the intestinal tract. Because it utilizes an alternate chloride channel, lubiprostone may be especially effective for constipation in patients with CF. CONCLUSIONS: Lubiprostone provides an additional option for the treatment of constipation in adults with CF. Its use in the CF population deserves further study.

Persistent Adherence to Airway Clearance Therapy in Adults With Cystic Fibrosis.

BACKGROUND: Airway clearance therapy (ACT) is a core component of daily treatment for cystic fibrosis (CF). However, surprisingly little is known about sustained or persistent use of ACT over time among adults with CF. This longitudinal study examined persistent adherence to ACT over 12 months and its modifiable predictors, drawing on aspects of Social Cognitive Theory and the Theory of Planned Behavior. METHODS: Subjects were drawn from a regional CF center in the southern United States. Predictor variables evaluated at baseline included self-efficacy for ACT (ie, self-confidence in overcoming barriers), outcome expectations (ie, perceived necessity of ACT and concerns about its disruptive effects), and subjective norms (ie, perceptions of being influenced by others). The Cystic Fibrosis Treatment Questionnaire (CFTQ) was used to assess self-reported adherence to ACT at baseline, at 6 months, and at 12 months. RESULTS: The mean age of subjects was 27.2 ± 9.1 y, and mean FEV1% predicted was 65.5 ± 24.8. Forty-six percent of subjects reported persistent use of ACT (classified as adherent at all assessment periods). In bivariate analyses, all social cognitive predictor variables assessed at baseline were significantly related to persistent adherence (all P < .03), except subjective norms. In logistic regression analyses that modeled the effects of these predictors simultaneously while controlling for FEV1%, fewer baseline concerns about ACT (odds ratio = 0.82, 95% CI 0.69-0.99) and greater self-efficacy (odds ratio = 1.09, 95% CI 1.01-1.18) remained significant independent predictors. CONCLUSIONS: This longitudinal study addresses an important gap in the literature regarding adherence to ACT over time (12 mo) in a routine clinical setting. Persistent adherence was problematic. As anticipated, social cognitive variables (self-confidence and perceived concerns) predicted self-reported persistence, and these may represent practical targets for intervention.

Effectiveness of essential amino acid supplementation in stimulating whole body net protein anabolism is comparable between COPD patients and healthy older adults.

BACKGROUND: The development of effective nutritional strategies in support of muscle growth for patients with chronic obstructive pulmonary disease (COPD) remains challenging. Dietary essential amino acids (EAAs) are the main driver of postprandial net protein anabolism. In agreement, EAA supplements in healthy older adults are more effective than supplements with the composition of complete proteins. In patients with COPD it is still unknown whether complete protein supplements can be substituted with only EAAs, and whether they are as effective as in healthy older adults. METHODS: According to a double-blind randomized crossover design, we examined in 23 patients with moderate to very severe COPD (age: 65±2 years, FEV1: 40±2% of predicted) and 19 healthy age-matched subjects (age: 64±2 years), whether a free EAA mixture with a high proportion (40%) of leucine (EAA mixture) stimulated whole body net protein gain more than a similar mixture of balanced free EAAs and non-EAAs as present in whey protein (TAA mixture). Whole body net protein gain and splanchnic extraction of phenylalanine (PHE) were assessed by continuous IV infusion of L-[ring-2H5]-PHE and L-[ring-2H2]-tyrosine, and enteral intake of L-[15N]-PHE (added to the mixtures). RESULTS: Besides an excellent positive linear relationship between PHE intake and net protein gain in both groups (r=0.84-0.91, P<0.001), net protein gain was 42% higher in healthy controls and 49% higher in COPD patients after intake of the EAA mixture compared to the TAA mixture (P<0.0001). These findings could not be attributed to the high LEU content, as in both groups net protein gain per gram EAA intake was lower for the EAA mixture (P<0.0001). Net protein gain was higher in COPD patients for both mixtures due to a 40% lower splanchnic extraction (P<0.0001), but was similarly related to dietary PHE (i.e. EAA) plasma appearance. CONCLUSIONS: In COPD patients, similarly to healthy older adults, free EAA supplements stimulate whole body protein anabolism more than free amino acid supplements with the composition of complete proteins. Therefore, free EAA supplements may aid in the prevention and treatment of muscle wasting in this patient population.

Alterations in whole-body arginine metabolism in chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a condition characterized by systemic low-grade inflammation that could increase the production of nitric oxide (NO), of which arginine is the sole precursor. Arginine is derived from the breakdown of protein and through the conversion of citrulline to arginine (de novo arginine production). OBJECTIVE: Our objective was to study whole-body arginine and citrulline and related metabolism in stable COPD patients. DESIGN: With the use of stable isotope methodology, we studied whole-body arginine and citrulline rates of appearance, de novo arginine (citrulline-to-arginine flux) and NO (arginine-to-citrulline flux) production, protein synthesis and breakdown rates, and plasma amino acid concentrations in a heterogeneous group of patients with moderate-to-severe COPD [n = 23, mean ± SE age: 65 ± 2 y, forced expiratory volume in 1 s (FEV1): 40% ± 2% of predicted], and a group of healthy older adults (n = 19, mean ± SE age: 64 ± 2 y, FEV1: 95% ± 4% of predicted). RESULTS: Although plasma arginine and citrulline concentrations were comparable between COPD patients and controls, whole-body arginine (P = 0.015) and citrulline (P = 0.026) rates of appearance were higher in COPD patients and related to a 57% greater de novo arginine production (P < 0.0001). Despite a higher whole-body arginine clearance in COPD patients (P < 0.0001), we found no difference in NO production. CONCLUSION: In stable patients with moderate-to-severe COPD, endogenous arginine production is upregulated to support a higher arginine utilization that is unrelated to whole-body NO production. This trial was registered at clinicaltrials.gov as NCT01173354 and NCT01172314.

History of aerosol therapy: liquid nebulization to MDIs to DPIs.

Inhaled therapies have been used since ancient times and may have had their origins with the smoking of datura preparations in India 4,000 years ago. In the late 18th and in the 19th century, earthenware inhalers were popular for the inhalation of air drawn through infusions of plants and other ingredients. Atomizers and nebulizers were developed in the mid-1800s in France and were thought to be an outgrowth of the perfume industry as well as a response to the fashion of inhaling thermal waters at spas. Around the turn of the 20th century, combustible powders and cigarettes containing stramonium were popular for asthma and other lung complaints. Following the discovery of the utility of epinephrine for treating asthma, hand-bulb nebulizers were developed, as well as early compressor nebulizers. The marketing of the first pressurized metered-dose inhaler for epinephrine and isoproterenol, by Riker Laboratories in 1956, was a milestone in the development of inhaled drugs. There have been remarkable advances in the technology of devices and formulations for inhaled drugs in the past 50 years. These have been influenced greatly by scientific developments in several areas: theoretical modeling and indirect measures of lung deposition, particle sizing techniques and in vitro deposition studies, scintigraphic deposition studies, pharmacokinetics and pharmacodynamics, and the 1987 Montreal Protocol, which banned chlorofluorocarbon propellants. We are now in an era of rapid technologic progress in inhaled drug delivery and applications of aerosol science, with the use of the aerosolized route for drugs for systemic therapy and for gene replacement therapy, use of aerosolized antimicrobials and immunosuppressants, and interest in specific targeting of inhaled drugs.

Hydrolyzed casein and whey protein meals comparably stimulate net whole-body protein synthesis in COPD patients with nutritional depletion without an additional effect of leucine co-ingestion.

BACKGROUND & AIMS: Muscle wasting commonly occurs in COPD, negatively affecting outcome. The aim was to examine the net whole-body protein synthesis response to two milk protein meals with comparable absorption rates (hydrolyzed casein (hCAS) vs. hydrolyzed whey (hWHEY)) and the effects of co-ingesting leucine. METHODS: Twelve COPD patients (GOLD stage II-IV) with nutritional depletion, were studied following intake of a 15 g hCAS or hWHEY protein meal with or without leucine-co-ingestion, according to a double-blind randomized cross-over design. The isotopic tracers L-[ring-(2)H5]-Phenylalanine, L-[ring-(2)H2]-Tyrosine, L-[(2)H3]-3-Methylhistidine (given via continuous intravenous infusion), and L-[(15)N]-Phenylalanine (added to the protein meals) were used to measure endogenous whole-body protein breakdown (WbPB), whole-body protein synthesis (WbPS), net protein synthesis (NetPS), splanchnic extraction and myofibrillar protein breakdown (MPB). Analyses were done in arterialized-venous plasma by LC/MS/MS. RESULTS: WbPS was greater after intake of the hCAS protein meal (P < 0.05) whereas the hWHEY protein meal reduced WbPB more (P < 0.01). NetPS was stimulated comparably, with a protein conversion rate greater than 70%. Addition of leucine did not modify the insulin, WbPB, WbPS or MPB response. CONCLUSIONS: Hydrolyzed casein and whey protein meals comparably and efficiently stimulate whole-body protein anabolism in COPD patients with nutritional depletion without an additional effect of leucine co-ingestion. This trial was registered at clinicaltrials.gov as NCT01154400.

Differences in physicians' self-reported knowledge of, attitudes toward, and responses to the black box warning on long-acting beta-agonists.

BACKGROUND: Inhaled corticosteroids and long-acting beta-agonists (LABAs) are recommended for treating moderate to severe persistent asthma. The Food and Drug Administration has issued a black box warning (BBW) for LABAs. OBJECTIVE: To investigate physician knowledge of the BBW and its effect on the practice of specialists (pulmonologists and allergists) and primary care physicians (PCPs) (internists and family physicians). METHODS: A total of 1,107 physicians responded to a questionnaire to determine their awareness of the BBW and whether it changed their practice. RESULTS: The group comprised 429 pulmonologists (38.8%), 395 allergists (35.7%), 141 internists (12.7%), 132 family physicians (11.9%), and 10 pediatricians (0.9%). Comparing specialists with PCPs, there was approximately a 10% difference in the rate of knowledge concerning the BBW (99.0% vs 90.8%, P < .001). Approximately a quarter of specialists agreed with the BBW compared with 52.9% of family physicians and 40.3% of internists. Twice as many PCPs vs specialists agreed with the warning (45.6% vs 24.2%, P < .001). The PCPs were more likely to alter their prescribing habits than were specialists (40.1% vs 34.6%, P < .005). Specialists were more likely to discuss the warning with patients than were PCPs (87.4% vs 64.8%, P < .001). For mild persistent asthma, most respondents chose inhaled corticosteroids as the preferred first-line therapy, but 11.4% of PCPs and 2.1% of specialists identified LABA monotherapy as their first choice. For moderate to severe asthma, the pattern of response was similar. CONCLUSION: Although most physicians were aware of the BBW for LABAs, there was a difference in how specialists and PCPs approached it and altered their prescribing habits.