Efficacy and Safety of Sublingual Cyclobenzaprine for the Treatment of Fibromyalgia: Results From a Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVE: To evaluate the efficacy and safety of TNX-102 SL, a once-nightly sublingual formulation of cyclobenzaprine, in reducing pain in patients with fibromyalgia (FM). METHODS: RELIEF was a double-blind, randomized, placebo-controlled trial. Overall, 503 patients received TNX-102 SL 2.8 mg for 2 weeks, followed by 5.6 mg for 12 weeks (248 patients), or matching placebo (255 patients). The primary end point was change from baseline at week 14 in the weekly average of daily pain scores. Secondary end points included Patient Global Impression of Change (PGIC) scores, Fibromyalgia Impact Questionnaire Revised (FIQR) scores, Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance and Fatigue scores, and daily sleep quality. Safety was assessed by adverse event (AE) reporting. RESULTS: Reduction in daily pain from baseline at week 14 was significantly greater with TNX-102 SL (least squares [LS] mean change -1.9 [95% confidence interval (95% CI) -2.1, -1.7]) versus placebo (LS mean change -1.5 [95% CI -1.7, -1.3]; P = 0.01). TNX-102 SL was not associated with significant improvement in PGIC at week 14 but was associated with improvements in FIQR scores, PROMIS scores, and daily sleep quality. Overall, 59.7% of patients receiving TNX-102 SL and 46.3% receiving placebo reported treatment-emergent AEs; the most common were oral hypoesthesia (17.3% with TNX-102 SL versus 0.4% with placebo), oral paresthesia (5.6% versus 0.4%, respectively), and product taste abnormal (4.4% versus 0.4%, respectively). CONCLUSION: In this phase III, randomized, controlled trial of patients with FM, treatment with TNX-102 SL was associated with significant reductions in daily pain and was safe and well tolerated.

A randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of a bupivacaine hydrochloride implant in patients undergoing abdominoplasty.

INTRODUCTION: Surgical site infiltration with bupivacaine hydrochloride (HCl) is a standard element of postoperative analgesia for soft tissue surgeries, but results in short-lived analgesia. A novel bupivacaine implant, XARACOLL (bupivacaine HCl), is Food and Drug Administration approved for treatment of acute postsurgical pain following adult inguinal herniorrhaphy. This study examined the efficacy and safety of the bupivacaine implant (300 mg) compared with placebo for postsurgical pain after abdominoplasty. METHODS: In this double-blind, placebo-controlled study, patients undergoing abdominoplasty were randomized to three 100 mg bupivacaine implants or three placebo collagen implants, in a 1:1 ratio, implanted intraoperatively. No other analgesics were administered into the surgical site. Patients were allowed opioids and acetaminophen for postoperative pain. Patients were followed for up to 30 days after treatment. PRIMARY OUTCOME: the analgesic effect of the bupivacaine implants through 24 hours postsurgery, measured by the sum of time-weighted pain intensity (SPI24). Prespecified key secondary outcomes included SPI48 and SPI72, percentage of opioid-free patients through 24, 48, and 72 hours, and adverse events, which were tested sequentially to control for multiplicity (ie, if the first variable failed to reach significance, no subsequent variables were declared statistically significant). RESULTS: The bupivacaine implant patients (n=181) reported statistically significant lower SPI24 (mean (SD) SPI24=102 (43), 95% CI 95 to 109) compared with placebo patients (n=184; SPI24=117 (45), 95% CI 111 to 123, p=0.002). SPI48 was 190 (88, 95% CI 177 to 204) for INL-001 and 206 (96, 95% CI 192 to 219) for placebo, and not significantly different between groups. The subsequent secondary variables were therefore declared not statistically significant. SPI72 was 265 (131, 95% CI 244 to 285) for INL-001 and 281 (146, 95% CI 261 to 301) for placebo. The opioid-free percentage of patients at 24, 48, and 72 hours was 19%, 17%, and 17% for INL-001 and 6.5% for placebo patients (at all timepoints). The only adverse event occurring in ≥5% of patients and for which proportion INL-001 >placebo was back pain (7.7% vs 7.6%). CONCLUSION: The study design was limited by not containing an active comparator. Compared with placebo, INL-001 provides postoperative analgesia that is temporally aligned with the period of maximal postsurgical pain in abdominoplasty and offers a favorable safety profile. TRIAL REGISTRATION NUMBER: NCT04785625.

Randomization tests in clinical trials with multiple imputation for handling missing data.

Randomization-based inference is a useful alternative to traditional population model-based methods. In trials with missing data, multiple imputation is often used. We describe how to construct a randomization test in clinical trials where multiple imputation is used for handling missing data. We illustrate the proposed methodology using Fisher's combining function applied to individual scores in two post-traumatic stress disorder trials.

Time to Onset of Response to Pitolisant for the Treatment of Excessive Daytime Sleepiness and Cataplexy in Patients With Narcolepsy: An Analysis of Randomized, Placebo-Controlled Trials.

BACKGROUND: Pitolisant is approved in the USA and Europe for the treatment of excessive daytime sleepiness or cataplexy in adults with narcolepsy. OBJECTIVE: Analyses evaluated the time to onset of clinical response during treatment with pitolisant. METHODS: Data were obtained from two randomized, double-blind, 7-week or 8-week, placebo-controlled studies (HARMONY 1, HARMONY CTP). Study medication was individually titrated to a maximum dose of pitolisant 35.6 mg/day and then remained stable. Efficacy assessments included the Epworth Sleepiness Scale and weekly rate of cataplexy (calculated from patient diaries). Onset of clinical response was defined as the first timepoint at which there was statistical separation between pitolisant and placebo. RESULTS: The analysis included 61 patients in HARMONY 1 (pitolisant, n = 31; placebo, n = 30) and 105 patients in HARMONY CTP (pitolisant, n = 54; placebo, n = 51). Onset of clinical response began at week 2 (HARMONY 1) or week 3 (HARMONY CTP) for the mean change in Epworth Sleepiness Scale score, and week 2 (HARMONY CTP) or week 5 (HARMONY 1) for the mean change in weekly rate of cataplexy, with further improvements observed in pitolisant-treated patients through the end of treatment. The percentage of treatment responders was significantly greater with pitolisant vs placebo beginning at week 3 for excessive daytime sleepiness (defined as an Epworth Sleepiness Scale score reduction ≥ 3) and week 2 for cataplexy (defined as a ≥ 50% reduction in weekly rate of cataplexy [HARMONY CTP]). CONCLUSIONS: Onset of clinical response for excessive daytime sleepiness and/or cataplexy was generally observed within the first 2-3 weeks of pitolisant treatment in patients with narcolepsy. CLINICALTRIALS. GOV IDENTIFIER: NCT01067222 (February 2010), NCT01800045 (February 2013).

Efficacy of pitolisant in patients with high burden of narcolepsy symptoms: pooled analysis of short-term, placebo-controlled studies.

STUDY OBJECTIVE: To evaluate the efficacy of pitolisant, a histamine 3 (H3)-receptor antagonist/inverse agonist, in adult patients with high burden of narcolepsy symptoms. METHODS: Data were pooled from two randomized, placebo-controlled, 7- or 8-week studies of pitolisant (titrated to a potential maximum dose of 35.6 mg/day) in adults with narcolepsy. Analyses included three independent patient subgroups: Epworth Sleepiness Scale (ESS) baseline score ≥16, Maintenance of Wakefulness Test (MWT) sleep latency ≤8 min, and ≥15 cataplexy attacks per week. RESULTS: The analysis populations included 118 patients for ESS (pitolisant, n = 60; placebo, n = 58), 105 for MWT (pitolisant, n = 59; placebo, n = 46), and 31 for cataplexy (pitolisant, n = 20; placebo, n = 11). On the ESS, least-squares mean change from baseline was significantly greater for pitolisant (-6.1) compared with placebo (-2.3; P < 0.001). Significantly more pitolisant-treated patients were classified as treatment responders: ESS score reduction ≥3, 69.0% in the pitolisant group versus 35.1% in the placebo group (P = 0.001); final ESS score ≤10, 36.2% versus 10.5%, respectively (P = 0.005). On the MWT, mean sleep latency increased from 3.5 min to 10.4 min with pitolisant and from 3.4 min to 6.8 min with placebo (P = 0.017). Least-squares mean change in the weekly rate of cataplexy was significantly greater for pitolisant (-14.5; baseline, 23.9; final, 9.4) compared with placebo (-0.1; baseline, 23.1; final, 23.0; P = 0.004). Headache was the most common adverse event with pitolisant. CONCLUSIONS: Pitolisant, at once-daily doses up to 35.6 mg, was efficacious for reducing excessive daytime sleepiness and cataplexy in patients with severe narcolepsy symptom burden.

Number Of Clinical Trial Study Sites Impacts Observed Treatment Effect Size: An Analysis Of Randomized Controlled Trials Of Opioids For Chronic Pain.

BACKGROUND: Many aspects of study conduct impact the observed effect size of treatment. Data were utilized from a recently published meta-analysis of randomized, double-blind, placebo-controlled, clinical trials performed for the United States Food and Drug Administration (FDA) approval of full mu-agonist opioids for the treatment of chronic pain. METHODS: The number of study sites in each clinical trial and standardized effect size (SES) were extracted and computed. Standardized effect size was plotted against number of sites, and a two-piece linear model was fit to the plot. Ten studies were included. RESULTS: The SES decreased linearly by 0.13 units for every 10 sites (p=0.037), from 0.75 to 0.36, until an inflection point of 60 sites, after which SES did not decline further. The total number of subjects required for 90% power to discriminate drug from placebo increased from 78 to 336 subjects going from 30 to 60 sites. CONCLUSION: Results showed that the number of sites was a source of loss of assay sensitivity in clinical trials, which may contribute to the well-known problem of failure to successfully transition from Phase 2 to Phase 3 clinical development. Potential solutions include minimizing the number of sites, more rigorous and validated training, central statistical monitoring with rapid correction of performance issues, and more rigorous subject and site selection.

Analgesic efficacy, safety, and tolerability of a long-acting abuse-deterrent formulation of oxycodone for moderate-to-severe chronic low back pain in subjects successfully switched from immediate-release oxycodone.

OBJECTIVES: This post hoc analysis of data from a randomized, double-blind, placebo-controlled, enriched-enrollment randomized-withdrawal Phase III study evaluated the safety, tolerability, and analgesic efficacy of Oxycodone DETERx extended-release (ER), abuse-deterrent capsules (Xtampza® ER) in subjects with chronic low back pain who were successfully transitioned from immediate-release (IR) oxycodone. METHODS: Continuous outcomes were analyzed using a mixed-model repeated-measures approach; binomial outcomes were analyzed using chi-squared; and time-to-event outcomes using Kaplan-Meier analyses. RESULTS: A total of 110 subjects previously prescribed IR oxycodone entered the Open-label Titration Phase. Forty-four subjects were randomized to Oxycodone DETERx (n=22) or placebo (n=22) in the 12-week Double-blind Maintenance Phase. Efficacy results in this subgroup showed a statistically significant difference between Oxycodone DETERx and placebo in average pain intensity scores from Randomization Baseline to Week 12 (least squares mean [± standard error], -1.88 [0.70]; P=0.0078). Additional efficacy results indicated that Oxycodone DETERx vs placebo was associated with a statistically significant benefit in durability of effect from Week 2 through Week 12 (P<0.01), numbers of subjects with a ≥30% (n [%] 10 [45.5%] vs 0 [0%]; P=0.0004) and ≥50% (10 [45.5%] vs 0 [0%]; P=0.0004) improvement in pain intensity, longer time-to-exit (P=0.0014), a greater number of subjects who completed the study (14 [63.6%] vs 4 [18.2%]), and less rescue medication use (acetaminophen; mean [SD], 163.5 [337.8] mg) vs 216.2 [377.3] mg). Adverse event profiles were consistent with opioid class effects and results from the original study; Oxycodone DETERx was well tolerated in subjects previously treated with short-acting oxycodone. CONCLUSIONS: Oxycodone DETERx resulted in clinically meaningful and statistically significant efficacy in subjects with chronic low back pain who were previously prescribed IR oxycodone and were successfully switched to ER Oxycodone DETERx.

Tolerability, Safety, and Effectiveness of Oxycodone DETERx in Elderly Patients ≥65 Years of Age with Chronic Low Back Pain: A Randomized Controlled Trial.

TRIAL DESIGN: This was a phase III, randomized withdrawal, double-blind, placebo-controlled, enriched enrollment, parallel-group, multicenter study intended to demonstrate the safety, tolerability, and analgesic efficacy of oxycodone DETERx® (Xtampza™ ER) compared with matching placebo. METHODS: This post hoc analysis was performed using data from a subpopulation of enrolled patients who were ≥65 years of age. The study enrolled male and female patients with a clinical diagnosis of moderate-to-severe chronic low back pain for a minimum of 6 months prior to screening who required around-the-clock opioid therapy. To be eligible for enrollment, patients were required to have an average 24-h pain intensity score of ≥5 and ≤9 on an 11-point (0-10) Pain Intensity-Numerical Rating Scale at the screening visit. The study enrolled both opioid-experienced and opioid-naïve patients. The study consisted of an open-label titration phase followed by a 12-week double-blind maintenance phase. The dose range was 40-160 mg oxycodone hydrochloride equivalent per day. This post hoc analysis evaluated the safety, tolerability, and effectiveness of oxycodone DETERx among patients ≥65 years of age. The effectiveness of oxycodone DETERx was evaluated based on average pain intensity scores, Patient Global Impression of Change, responder analysis, and Kaplan-Meier survival analysis. The safety and tolerability of oxycodone DETERx were also evaluated. Patients were randomized to either oxycodone DETERx or placebo using a blocked randomization scheme in a 1:1 ratio. Randomization was stratified by previous opioid use (naïve or experienced). The study drug was coded in a manner that maintained the blinding. Study personnel and patients remained blinded to the assigned treatments throughout the study. RESULTS: For this post-hoc analysis, the intent-to-treat and randomized safety populations included 52 patients ≥65 years old, 26 each in the oxycodone DETERx and placebo groups, who participated in the study during the titration phase and were randomized to the double-blind maintenance phase. Clinically important pain reduction from screening was achieved with oxycodone DETERx, with the median pain intensity score decreasing from 7.50 at screening to 2.69 at Week 12. A clinically meaningful treatment difference of -0.9 in pain score between oxycodone DETERx and placebo was observed. All 18 elderly patients who completed the study reported improvement in pain, with 62% showing ≥30% improvement and 54% showing ≥50% improvement in pain intensity compared with patients on placebo (p = 0.0128 and p = 0.0501, respectively). Patients on oxycodone DETERx remained in the study longer than those on placebo. Of the 26 patients ≥65 years old randomized to continue oxycodone DETERx during the double-blind maintenance phase, 18 (69%) completed the study; only two patients (8%) in the oxycodone DETERx group discontinued due to adverse events. The safety and tolerability profiles showed no new or unexpected safety concerns. The adverse event profiles were similar between the titration and double-blind maintenance phases. CONCLUSIONS: Oxycodone DETERx was efficacious and generally well tolerated in patients ≥65 years old. TRIAL REGISTRATION: The study was registered with ClinicalTrials.gov (NCT01685684).

Evaluation of the durability of pain relief throughout a 12 hour dosing interval of a novel, extended-release, abuse-deterrent formulation of oxycodone.

BACKGROUND: Abuse deterrent formulations (ADF) are designed to prevent the misuse of opioids by tampering (e.g. physical and chemical manipulation) in order to ingest the opioid in a manner other than intended. Extended-release (ER) formulations are formulated with a larger drug load than immediate-release (IR) formulations, which makes ER opioids more desirable to drug abusers than I.R. formulations. ADFs, therefore, are particularly useful with ER opioid agents, which are designed to produce consistent analgesia over prolonged dosing intervals. However, the drug release properties of these formulations vary and sometimes may not provide adequate pain relief throughout the intended dosing interval, requiring patients to take additional medication for pain relief. Oxycodone DETERx* (Xtampza ER * ) is a novel, microsphere-in-capsule opioid formulation, which allows for twice daily dosing (i.e. every 12 hours) and mitigates the ability to tamper with the formulation. OBJECTIVE: To evaluate the durability of pain relief of a novel formulation of oxycodone throughout the 12 hour dosing interval. RESEARCH DESIGN AND METHODS: This study is a post-hoc analysis of 193 subjects in a Phase 3 randomized withdrawal, double-blind, placebo-controlled, enriched-enrollment, parallel-group, multicenter, 12-week clinical study. MAIN OUTCOME MEASURES: The analysis evaluated the frequency and distribution of use of oxycodone ER and rescue medication during the Double-blind Maintenance Phase of the study. RESULTS: Usage patterns captured by an electronic diary indicated limited overall and limited per-day use of rescue medication with no increase in rescue medication consumption 8 to 12 hours post-dose, suggesting that subjects did not experience end-of-dose failure during this time period. LIMITATIONS: This study is limited in that it is a post-hoc analysis based on data gathered electronically from a large, prospective, double-blind, randomized, placebo-controlled, Phase 3 clinical study. CONCLUSION: The evaluation of dosing patterns indicates that this ER oxycodone capsule formulation has durability of effect over the entire 12-hour dosing interval. These data support the use of abuse-deterrent oxycodone ER as a 12-hour dosing formulation.

Differential effects of outdoor versus indoor fungal spores on asthma morbidity in inner-city children.

BACKGROUND: Although sensitization to fungal allergens is prevalent in inner-city children with asthma, the relationship between fungal exposure and morbidity is poorly understood. OBJECTIVE: We examined relationships between fungal sensitization, exposure, and asthma morbidity in inner-city children. METHODS: Participants were 5 to 11 years old and enrolled in the Inner-City Asthma Study. This report includes the subset of children with at least 1 positive skin test (PST) response to a fungal allergen extract; for these children, indoor and outdoor airborne culturable fungi levels were measured at baseline and throughout the 2-year study. Asthma morbidity measures were collected prospectively. The primary outcome was symptom days per 2 weeks. RESULTS: At baseline, children with a PST response to a fungal allergen extract had significantly more symptom days compared with those without a PST response to any fungal allergen extract (6.3 vs 5.7 days per 2 weeks, P = .04). During the study, increases in total fungal exposure and indoor Penicillium species exposure were associated with increases in symptom days and asthma-related unscheduled visits. Indoor exposures to total fungi and to Penicillium species were associated with significant increases in unscheduled visits, even after controlling for outdoor fungal levels. Adverse effects associated with exposure to a specific fungus were stronger among children with PST responses to that fungal allergen extract compared with those seen in children with negative skin test responses. CONCLUSION: Outdoor fungal exposure is primarily associated with increased asthma symptoms and increased risk of exacerbations in this population.

Cockroach allergen reduction by cockroach control alone in low-income urban homes: a randomized control trial.

BACKGROUND: We previously reported significant reductions in cockroach allergen concentrations in urban homes by reducing cockroach infestations. OBJECTIVE: To determine the effectiveness of pest control performed by professional entomologists, compared with commercial companies, in reducing cockroach allergen. METHODS: This 3-arm randomized controlled trial enrolled 60 cockroach-infested homes in North Carolina. Homes were randomly assigned to a control group or 1 of 2 treatment groups. Treatment 1 had insecticide baits placed by entomologists from North Carolina State University. Treatment 2 received pest control from a randomly assigned commercial company. Vacuumed dust sampling and cockroach trapping were conducted at 0, 6, and 12 months. Dust samples were analyzed by ELISA. RESULTS: In treatment 1 homes, there were significant reductions in geometric mean trap counts compared with control and treatment 2 homes at 12 months. Relative to control, significant 12-month reductions in Bla g 1 were evident in treatment 1 homes at all sampled sites, except bedroom floor. From baseline to month 12, geometric mean Bla g 1 concentrations (U/g) decreased from 64.2 to 5.6 in kitchen, 10.6 to 1.1 in living room, 10.7 to 1.9 on bedroom floor, and 3.6 to 2.3 in bed. Treatment 2 homes showed no significant 12-month allergen reductions versus control. CONCLUSION: Reductions in Bla g 1 in cockroach-infested homes can be achieved by reducing infestations; however, the magnitude of allergen reduction is dependent on the thoroughness and effectiveness of cockroach eradication efforts. CLINICAL IMPLICATIONS: Elimination of cockroaches is an effective method for reducing exposure to cockroach allergen.

Asthma cases attributable to atopy: results from the Third National Health and Nutrition Examination Survey.

BACKGROUND: The percentage of asthma cases attributable to atopy is the subject of debate. OBJECTIVES: The objectives were to estimate the percentage of asthma cases in the US population attributable to atopy and to examine associations between allergen-specific skin tests and asthma. METHODS: Data were obtained from the Third National Health and Nutrition Examination Survey, in which subjects age 6 to 59 years were skin tested with 10 allergens. Atopy was defined as at least 1 positive allergen-specific test. Doctor-diagnosed current asthma was assessed by questionnaire. RESULTS: In the United States, 56.3% of the asthma cases were attributable to atopy, and that percentage was greater among males than females, among persons in the highest education category than in lower education categories, and among persons living in highly populated metropolitan areas than in all other areas. Each allergen-specific test was strongly associated with asthma before adjustment (odds ratios varied from 2.1 to 4.5); however, after adjustment by all the allergens, only tests to cat, Alternaria, white oak, and perennial rye were independently associated with asthma. Perennial rye was inversely associated with asthma. Of the 10 allergens, a positive response to cat accounted for the highest percentage of asthma cases (29.3%). CONCLUSION: About half of the current asthma cases in the US population represented by the Third National Health and Nutrition Examination Survey were attributable to atopy. Some allergen-specific skin tests were not independently associated with asthma. CLINICAL IMPLICATIONS: If atopy could be prevented or reversed, or its effect on asthma blocked, then a large percentage of asthma cases in the US population could be prevented.

Oral pathogens and allergic disease: results from the Third National Health and Nutrition Examination Survey.

BACKGROUND: The hygiene hypothesis contends that fewer opportunities for infection have led to increases in the prevalences of asthma and other allergic diseases. OBJECTIVE: This study evaluated the association between asthma, wheeze, and hay fever and antibodies to 2 oral bacteria associated with periodontal disease. METHODS: Data were obtained from the Third National Health and Nutrition Examination Survey. Serum levels of IgG antibodies to Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis were quantified by enzyme-linked immunoassays in 9385 subjects age 12 years and older. The outcomes were current asthma, wheeze, and hay fever. Odds ratios (ORs) representing a 1-log-unit increase in IgG concentrations were estimated with logistic regression. ORs were adjusted for 8 confounders and weighted to represent the US population. RESULTS: For each disease outcome, geometric mean antibody concentrations were higher in persons without the disease outcome than with the disease outcome. For a 1-log-unit increase in P gingivalis antibody concentration, adjusted ORs were 0.41 (95% CI, 0.20-0.87) for asthma, 0.43 (0.23-0.78) for wheeze, and 0.45 (0.23-0.93) for hay fever. For A actinomycetemcomitans, those ORs were 0.56 (0.19-1.72), 0.39 (0.17-0.86), and 0.48 (0.23-1.03), respectively. CONCLUSION: Consistent with the hygiene hypothesis, higher concentrations of IgG antibodies to P gingivalis were significantly associated with lower prevalences of asthma, wheeze, and hay fever, and higher concentrations of IgG antibodies to A actinomycetemcomitans were significantly associated with a lower prevalence of wheeze. CLINICAL IMPLICATIONS: Colonization of the oral cavity by bacteria and other microbes might play a protective role in the etiology of allergic disease.

Comparison of enzyme immunoassay-based assays for environmental Alternaria alternata.

BACKGROUND: Alternaria alternata-derived allergenic materials are causes of human disease. Several immunoassays exist to quantify these materials. OBJECTIVE: To compare methods for evaluating Alternaria content. METHODS: Four methods, including 1 monoclonal antibody (MAb)-based assay specific for recombinant Alt a 1, 1 MAb-based assay for chromatographically purified Alt a 1, 1 polyclonal antibody (PAb)-based assay for chromatographically purified Alt a 1, and 1 PAb-based assay for whole Alternaria extract, were evaluated. Environmental samples collected as part of the National Survey of Lead and Allergens in Housing were examined. Alternaria spore counts were determined in dust by observation. RESULTS: The MAb-based assay for recombinant Alt a 1 detected Alternaria in few samples (25%); the PAb-based assay for whole Alternaria proteins detected antigen in 97% of the samples. The PAb- and MAb-based assays for purified Alt a 1 detected antigen in 100% of the samples. There was a significant positive correlation between the 2 assays directed against purified Alt a 1. There was a positive correlation between the PAb-based assay for whole Alternaria and the PAb-based assay for Alt a 1. Nearly all the dust samples contained Alternaria spores, and there was a strong positive correlation between counts and all assays. CONCLUSION: Because of the multifaceted nature of Alternaria, the disparities between methods for quantifying Alternaria, the cross-reactivity between fungal allergens, and the documented genetic promiscuity of this fungus, enzyme immunoassays using PAbs against a range of Alternaria proteins will probably produce the most reliable estimation of overall Alternaria exposure in house dust.

Feasibility of using subject-collected dust samples in epidemiologic and clinical studies of indoor allergens.

Studies of indoor allergen exposures are often limited by the cost and logistics of sending technicians to homes to collect dust. In this study we evaluated the feasibility of having subjects collect their own dust samples. The objectives were to compare allergen concentrations between subject- and technician-collected samples and to examine the sample return rate. Using a dust collection device and written instructions provided to them by mail, 102 subjects collected a combined dust sample from a bed and bedroom floor. Later the same day, a technician collected a side-by-side sample. Dust samples were weighed and analyzed for the cat allergen Fel d 1 and the dust mite allergen Der p 1. Fifty additional subjects who were enrolled by telephone were mailed dust collection packages and asked to return a dust sample and questionnaire by mail. A technician did not visit their homes. Correlations between subject- and technician-collected samples were strong for concentrations of Fel d 1 (r = 0.88) and Der p 1 (r = 0.87). With allergen concentrations dichotomized at lower limits of detection and clinically relevant thresholds, agreements between methodologies ranged from 91 to 98%. Although dust weights were correlated (r = 0.48, p < 0.001), subjects collected lighter samples. Among the group of 50 subjects, 46 returned a dust sample and completed questionnaire. The median number of days to receive a sample was 15. With some limitations, subject-collected dust sampling appears to be a valid and practical option for epidemiologic and clinical studies that report allergen concentration as a measure of exposure.

Abatement of cockroach allergens (Bla g 1 and Bla g 2) in low-income, urban housing: month 12 continuation results.

BACKGROUND: In the first 6 months of this previously published, randomized trial, the combined intervention of occupant education, insecticide bait application, and professional cleaning significantly reduced cockroach numbers and Bla g 1 allergen levels in inner-city homes. OBJECTIVE: This continuation study investigated whether the cockroach allergen reductions achieved by month 6 could be maintained through month 12 with insecticide application alone. METHODS: Because we had agreed to place insecticide bait in control homes at the conclusion of the first study, intervention and control homes were treated with insecticide bait at months 6 and 9. No other intervention was conducted in either arm. Vacuumed dust and swab samples were collected at month 12. Twenty-one of the 31 original homes completed the 12-month study. RESULTS: Among the original intervention homes, Bla g 1 concentrations remained essentially unchanged from months 6 to 12. However, among the crossed-over control homes, the geometric mean Bla g 1 concentrations (Units per gram of dust) decreased from 287 to 14.4 for kitchen floors (95% reduction), from 28.8 to 5.6 for living room floors/sofas (81% reduction), from 26.7 to 4.7 for bedroom floors (82% reduction), and from 7.2 to 2.4 for beds (67% reduction). At month 12, Bla g 1 concentrations did not significantly differ between intervention and crossed-over control homes (P >.64 at each location). Similar results were seen for the allergen Bla g 2. CONCLUSIONS: Reductions in cockroach allergen concentrations achieved through the combined intervention of occupant education, insecticide application, and professional cleaning can be maintained with continued cockroach control. Surprisingly, and in contrast to other studies, insecticide application alone significantly lowered allergen concentrations in the crossed-over control homes. This unexpected result is being tested further in another randomized trial.

Abatement of cockroach allergen (Bla g 1) in low-income, urban housing: A randomized controlled trial.

BACKGROUND: Clinically relevant reductions in exposure to cockroach allergen, an important risk factor for asthma in inner-city households, have proven difficult to achieve in intervention trials. OBJECTIVE: This study investigated a method for the abatement of cockroach allergen in low-income, urban homes. The goal was to reduce mean Bla g 1 concentrations below the previously proposed thresholds for allergic sensitization and asthma morbidity. METHODS: A prerandomized, nonmasked trial with 16 intervention and 15 control homes was conducted. Study inclusion was based on 50 to 500 cockroaches trapped in a 3-day period. The interventions consisted of occupant education, placement of insecticide bait, and professional cleaning. Vacuumed dust and multiple swab samples were collected at 0, 1, 2, 4, and 6 months in intervention homes and at 0 and 6 months in control homes. Room maps containing cockroach and allergen data were used to guide and monitor the interventions. RESULTS: From 0 to 6 months among intervention homes, geometric mean Bla g 1 concentrations (U/g dust) decreased from 633 to 24 on kitchen floors (96% reduction), from 25 to 4.3 on living room floors/sofas (83% reduction), from 46 to 7.3 on bedroom floors (84% reduction), and from 6.1 to 1.0 in bedroom beds (84% reduction). These reductions, with the exception of that on the bedroom floor (P =.06), were statistically significant relative to changes in control homes. CONCLUSIONS: Substantial reductions in cockroach allergen levels can be achieved in inner-city homes. In this study, allergen levels were reduced below the sensitization threshold (2 U/g) in beds, arguably the most relevant site for exposure, and below the asthma morbidity threshold (8 U/g) on bedroom floors and living room floors/sofas. The level on kitchen floors, although reduced 96%, remained above the asthma morbidity threshold. Future studies will test the intervention's effectiveness in asthma prevention trials.

Particle concentrations in inner-city homes of children with asthma: the effect of smoking, cooking, and outdoor pollution.

Inner-city children have high rates of asthma. Exposures to particles, including allergens, may cause or exacerbate asthma symptoms. As part of an epidemiologic study of inner-city children with asthma, continuous (10-min average) measurements of particle concentrations were made for 2-week periods in 294 homes drawn from seven cities. Measurements were made using an optical scattering device that is most sensitive to fine particles. The concentrations recorded by these devices were corrected to agree with colocated outdoor gravimetric PM2.5 monitors. Indoor concentrations in the homes averaged 27.7 (standard deviation = 35.9) micro g/m3, compared with concurrent outdoor concentrations of 13.6 (7.5) micro g/m3. A multivariate model indicated that outdoor particles penetrated indoors with an efficiency of 0.48 and were therefore responsible for only 25% of the mean indoor concentration. The major indoor source was smoking, which elevated indoor concentrations by 37 micro g/m3 in the 101 homes with smokers. Other significant sources included frying, smoky cooking events, use of incense, and apartment housing, although the increases due to these events ranged only from 3 to 6 micro g/m3. The 10-min averaging time allowed calculation of an average diurnal variation, showing large increases in the evening due to smoking and smaller increases at meal times due to cooking. Most of the observed variance in indoor concentrations was day to day, with roughly similar contributions to the variance from visit to visit and home to home within a city and only a small contribution made by variance among cities. The small variation among cities and the similarity across cities of the observed indoor air particle distributions suggest that sources of indoor concentrations do not vary considerably from one city to the next, and thus that simple models can predict indoor air concentrations in cities having only outdoor measurements.