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HELMINTH INFECTION AND ALLERGIC SENSITIZATION IN ESWATI CHILDREN
Abstracts: Poster Sessions / Ann Allergy Asthma Immunol 121 (2018) S22−S62
P351 HELMINTH INFECTION AND ALLERGIC SENSITIZATION IN ESWATI CHILDREN N. Ramsey*,1, A. DiNardo2, C. Lupinek3, T. Nishiguci2, R. Kiss3, G. Mtetwa4, B. Mzileni4, A. Kay4, W. Secpr*,5, R. Mejia2, C. Davis2, R. Valenta3, J. Orange1, P. Hotez2, A. Mandalakas2, 1. New York, NY; 2. Houston, TX; 3. Vienna, Austria; 4. Mbabane, Swaziland; 5. Atlanta, GA Introduction: The link between helminth infection and allergic conditions is complex and the two conditions have been noted to be both indirectly and directly related. Here we describe helminth infection, allergic symptoms, environmental exposures, and allergen sensitization among patients at a clinic in Mbabane, Swaziland. Methods: Participants are enrolled in a longitudinal umbrella study which houses the nested case control study presented here. Allergic symptoms are defined by clinician H&P, and interviewer-guided modified International Survey on Allergies and Asthma in Childhood survey in Siswati. Environmental exposures were identified using interviewer-guided survey in Siswati. IgE sensitization to more than 160 allergen molecules was detected using ImmunoCAP ISAC technology. Results: On average patients were 8 years old and 44% were male. Nineteen percent (38/188) of participants have current helminth infection and 8% (15/188) have remote helminth infection. Sixtyeight percent (128/188) of participants surveyed were positive for one or more allergic symptom. Eczema/rash was more prevalent in children with exposure to a miner in the home. Remotely infected patients had less allergy symptoms. House dust mite allergens were the most common allergens recognized in this population 28% (45/ 160). Allergen sensitization was strikingly absent or low in patients with helminth infection. Conclusions: Our evidence suggests that allergic symptoms are common in this population and allergies are less likely among patients with remote helminth infection. There is a dampening of allergen sensitization in patients with helminth infection and allergy symptoms in patients with remote helminth infection. These results support the hygiene hypothesis, in part, and further elucidate its complexities.
P352 SUBCUTANEOUS SELF-ADMINISTRATION OF LANADELUMAB FOR PROPHYLACTIC TREATMENT IN PATIENTS WITH HEREDITARY ANGIOEDEMA (HAE) W. Lumry*,1, P. Busse2, P. Lu3, G. Jain3, C. Nurse3, M. Maurer4, 1. Dallas, TX; 2. New York, NY; 3. Lexington, MA; 4. Berlin, Germany Introduction: Administration of a large C1 inhibitor (C1-INH) volume twice weekly for prophylaxis can be burdensome. Lanadelumab, a monoclonal antibody targeting plasma kallikrein, effectively prevents attacks in patients with HAE type I/II. Patients’ self-administration experience was investigated. Methods: Interim data (May 2016-September 2017) from an ongoing open-label extension study (NCT02741596) on attack rates and injection site reactions (ISRs) in rollover patients from a phase 3 study (after their second dose) and non-rollover patients who received 300 mg (2 mL) subcutaneous (SC) lanadelumab every 2 weeks (Q2W) via self-administration versus administration by study staff were compared. Trained patients (aged ≥ 12 years) self-administered lanadelumab (at home or in-clinic) after two administrations by staff. Patients with intravenous C1-INH experience indicated their preferred administration route in a survey. Results: In 212 patients, 56.4% of 3157 doses were self-administered. Of 209 patients who received ≥ 1 dose, ≥ 80% of doses were administered by staff versus self-administered in 61 versus 97 patients; mean (SD) attack rate reductions were -2.1 (1.98) and -3.3 (2.58) attacks/ month, respectively. The proportion of doses causing ISRs postadministration by staff, self-administration at home and in-clinic
S57
were 19.4%, 21.5%, and 16.9%, respectively. At day 266, 70.9% versus 7.3% of 55 patients preferred SC over intravenous administration and 59.3% and 52.5% of 59 patients reported that SC injections were easier to administer and convenient, respectively. Conclusions: Patients successfully self-administered SC lanadelumab (300 mg Q2W) to prevent HAE attacks effectively with no difference in efficacy or ISRs compared with patients who received doses by inclinic staff.
P353 A SEMI-AUTOMATED APPROACH TO IDENTIFYING CHRONIC COUGH IN ELECTRONIC HEALTH RECORDS M. Weiner1, J. Weaver*,2, P. Dexter1, A. Roberts1, Z. Liu1, S. Hui1, A. Church1, I. DOSHI3, K. Heithoff2, 1. Indianapolis, IN; 2. Kenilworth, NJ; 3. RAHWAY, NJ Introduction: Chronic cough (CC) of eight or more weeks affects up to 10% of adults and may lead to expensive treatments and reduced quality of life. Incomplete diagnostic coding complicates identifying CC in electronic health records (EHRs). Natural language processing (NLP) of EHR text could improve CC detection. Objective: Assess NLP as a method to identify CC in EHRs. Methods: Coded and text-based data from a Midwestern EHR were used to identify patients aged 18-85 during 2005-2015. NLP evaluated all text notes except prescriptions and patient instructions, for mentions of cough or expectoration. Filtering based on output review was performed: after initial cohort identification, two clinicians and a biostatistician reviewed twelve sets of 50 records each, with iterative refinements, until the positive predictive value exceeded 90%. NLP, ICD-10, or cough medication identified cough encounters. Three encounters spanning at least 56 days within 120 days defined CC. Results: Optimization of NLP required identifying and eliminating cough denials, general instructions, and historical references. Of 260,517 cough encounters, 23% had a diagnostic code or medication indicating cough. Encounters identified 25,767 patients (62% women) with CC. NLP alone identified 74%; diagnoses or medications alone identified 14%. The positive predictive value was 97%. Conclusions: Most cohort patients were identified through NLP alone, rather than diagnoses or medications. NLP improved detection of patients nearly seven-fold, addressing the gap in ability to identify and characterize CC disease burden. Identifying these patients is important for characterizing their treatment and unmet needs. Pharmacology and Pharmacotherapeutics
P400 THE EFFECTS OF FREEZING ON EPINEPHRINE AUTO-INJECTOR DEVICE FUNCTION A. Cooper*, J. Brown, P. Qu, Seattle, WA Introduction: Epinephrine auto-injectors (EAIs) typically require storage temperatures between 20-25°C with permitted excursions between 15°-30°C. However, previous studies suggest that freezing does not degrade epinephrine, and in one study 10 frozen and thawed EAIs fired successfully. We aim to further explore the effects of freezing on EAI function. Methods: For 104 paired same-lot post-consumer single-commonbrand expired EAIs (50 0.3 mg and 50 0.15 mg devices), one of the pair was frozen at -25°C for 24 hours while the other was kept at recommended temperatures (control). After thawing the frozen device, both devices were fired into meat. The increase in meat mass and decrease in device mass were measured to estimate the mass of solution fired. Results: There was sufficient power (>95%) to conclude equivalence for both outcomes, defined as equivalent if the average difference in mass for frozen devices was within 10% of the difference for unfrozen devices. Two one-sided t-tests showed equivalence for both
P351 HELMINTH INFECTION AND ALLERGIC SENSITIZATION IN ESWATI CHILDREN N. Ramsey*,1, A. DiNardo2, C. Lupinek3, T. Nishiguci2, R. Kiss3, G. Mtetwa4, B. Mzileni4, A. Kay4, W. Secpr*,5, R. Mejia2, C. Davis2, R. Valenta3, J. Orange1, P. Hotez2, A. Mandalakas2, 1. New York, NY; 2. Houston, TX; 3. Vienna, Austria; 4. Mbabane, Swaziland; 5. Atlanta, GA Introduction: The link between helminth infection and allergic conditions is complex and the two conditions have been noted to be both indirectly and directly related. Here we describe helminth infection, allergic symptoms, environmental exposures, and allergen sensitization among patients at a clinic in Mbabane, Swaziland. Methods: Participants are enrolled in a longitudinal umbrella study which houses the nested case control study presented here. Allergic symptoms are defined by clinician H&P, and interviewer-guided modified International Survey on Allergies and Asthma in Childhood survey in Siswati. Environmental exposures were identified using interviewer-guided survey in Siswati. IgE sensitization to more than 160 allergen molecules was detected using ImmunoCAP ISAC technology. Results: On average patients were 8 years old and 44% were male. Nineteen percent (38/188) of participants have current helminth infection and 8% (15/188) have remote helminth infection. Sixtyeight percent (128/188) of participants surveyed were positive for one or more allergic symptom. Eczema/rash was more prevalent in children with exposure to a miner in the home. Remotely infected patients had less allergy symptoms. House dust mite allergens were the most common allergens recognized in this population 28% (45/ 160). Allergen sensitization was strikingly absent or low in patients with helminth infection. Conclusions: Our evidence suggests that allergic symptoms are common in this population and allergies are less likely among patients with remote helminth infection. There is a dampening of allergen sensitization in patients with helminth infection and allergy symptoms in patients with remote helminth infection. These results support the hygiene hypothesis, in part, and further elucidate its complexities.
P352 SUBCUTANEOUS SELF-ADMINISTRATION OF LANADELUMAB FOR PROPHYLACTIC TREATMENT IN PATIENTS WITH HEREDITARY ANGIOEDEMA (HAE) W. Lumry*,1, P. Busse2, P. Lu3, G. Jain3, C. Nurse3, M. Maurer4, 1. Dallas, TX; 2. New York, NY; 3. Lexington, MA; 4. Berlin, Germany Introduction: Administration of a large C1 inhibitor (C1-INH) volume twice weekly for prophylaxis can be burdensome. Lanadelumab, a monoclonal antibody targeting plasma kallikrein, effectively prevents attacks in patients with HAE type I/II. Patients’ self-administration experience was investigated. Methods: Interim data (May 2016-September 2017) from an ongoing open-label extension study (NCT02741596) on attack rates and injection site reactions (ISRs) in rollover patients from a phase 3 study (after their second dose) and non-rollover patients who received 300 mg (2 mL) subcutaneous (SC) lanadelumab every 2 weeks (Q2W) via self-administration versus administration by study staff were compared. Trained patients (aged ≥ 12 years) self-administered lanadelumab (at home or in-clinic) after two administrations by staff. Patients with intravenous C1-INH experience indicated their preferred administration route in a survey. Results: In 212 patients, 56.4% of 3157 doses were self-administered. Of 209 patients who received ≥ 1 dose, ≥ 80% of doses were administered by staff versus self-administered in 61 versus 97 patients; mean (SD) attack rate reductions were -2.1 (1.98) and -3.3 (2.58) attacks/ month, respectively. The proportion of doses causing ISRs postadministration by staff, self-administration at home and in-clinic
S57
were 19.4%, 21.5%, and 16.9%, respectively. At day 266, 70.9% versus 7.3% of 55 patients preferred SC over intravenous administration and 59.3% and 52.5% of 59 patients reported that SC injections were easier to administer and convenient, respectively. Conclusions: Patients successfully self-administered SC lanadelumab (300 mg Q2W) to prevent HAE attacks effectively with no difference in efficacy or ISRs compared with patients who received doses by inclinic staff.
P353 A SEMI-AUTOMATED APPROACH TO IDENTIFYING CHRONIC COUGH IN ELECTRONIC HEALTH RECORDS M. Weiner1, J. Weaver*,2, P. Dexter1, A. Roberts1, Z. Liu1, S. Hui1, A. Church1, I. DOSHI3, K. Heithoff2, 1. Indianapolis, IN; 2. Kenilworth, NJ; 3. RAHWAY, NJ Introduction: Chronic cough (CC) of eight or more weeks affects up to 10% of adults and may lead to expensive treatments and reduced quality of life. Incomplete diagnostic coding complicates identifying CC in electronic health records (EHRs). Natural language processing (NLP) of EHR text could improve CC detection. Objective: Assess NLP as a method to identify CC in EHRs. Methods: Coded and text-based data from a Midwestern EHR were used to identify patients aged 18-85 during 2005-2015. NLP evaluated all text notes except prescriptions and patient instructions, for mentions of cough or expectoration. Filtering based on output review was performed: after initial cohort identification, two clinicians and a biostatistician reviewed twelve sets of 50 records each, with iterative refinements, until the positive predictive value exceeded 90%. NLP, ICD-10, or cough medication identified cough encounters. Three encounters spanning at least 56 days within 120 days defined CC. Results: Optimization of NLP required identifying and eliminating cough denials, general instructions, and historical references. Of 260,517 cough encounters, 23% had a diagnostic code or medication indicating cough. Encounters identified 25,767 patients (62% women) with CC. NLP alone identified 74%; diagnoses or medications alone identified 14%. The positive predictive value was 97%. Conclusions: Most cohort patients were identified through NLP alone, rather than diagnoses or medications. NLP improved detection of patients nearly seven-fold, addressing the gap in ability to identify and characterize CC disease burden. Identifying these patients is important for characterizing their treatment and unmet needs. Pharmacology and Pharmacotherapeutics
P400 THE EFFECTS OF FREEZING ON EPINEPHRINE AUTO-INJECTOR DEVICE FUNCTION A. Cooper*, J. Brown, P. Qu, Seattle, WA Introduction: Epinephrine auto-injectors (EAIs) typically require storage temperatures between 20-25°C with permitted excursions between 15°-30°C. However, previous studies suggest that freezing does not degrade epinephrine, and in one study 10 frozen and thawed EAIs fired successfully. We aim to further explore the effects of freezing on EAI function. Methods: For 104 paired same-lot post-consumer single-commonbrand expired EAIs (50 0.3 mg and 50 0.15 mg devices), one of the pair was frozen at -25°C for 24 hours while the other was kept at recommended temperatures (control). After thawing the frozen device, both devices were fired into meat. The increase in meat mass and decrease in device mass were measured to estimate the mass of solution fired. Results: There was sufficient power (>95%) to conclude equivalence for both outcomes, defined as equivalent if the average difference in mass for frozen devices was within 10% of the difference for unfrozen devices. Two one-sided t-tests showed equivalence for both