Patient-reported outcome measures in severe asthma: an expert consensus.

OBJECTIVE: The study aimed to reach a consensus on the most relevant patient-reported outcomes (PROs), the corresponding measures (PROMs), and measurement frequency during severe asthma patient follow-up. METHODS: Two Delphi rounds were conducted. The questionnaire was developed based on a systematic literature review, a focus group with patients, and a nominal group with experts. It assessed PROs' relevance and the appropriateness (A) and feasibility (F) of PROMs using a Likert scale (1=totally agree; 9=totally disagree). The consensus was established when ≥75% of participants agreed (1-3) or disagreed (7-9). RESULTS: Sixty-three professionals (25 hospital pharmacists, 14 allergists, 13 pulmonologists, and 11 nurses) and 5 patients answered the Delphi questionnaire. A consensus was reached on all PROs regarding their relevance. Experts agreed on the use of ACT (A:95.24%; F:95.24%), mini AQLQ (A:93.65; F:79.37%), mMRC dyspnea scale (A:85.71%; F:85.71%), TAI (A:92.06%; F:85.71%), MMAS (A:75.40%; F:82%), and the dispensing register (A:96.83%; F:92.06%). Also considered suitable were: SNOT-22 (A:90.48%; F:73.80%), PSQI (A:82.54; F:63.90%), HADS (A:82.54; F:64%), WPAI (A:77.78%; F:49.20%), TSQM-9 (A:79.37; F:70.50%) and knowledge of asthma questionnaire (A:77%; F:68.80%); however, their use in clinical practice was considered unfeasible. Panelists also agreed on the appropriateness of EQ-5D, which was finally included despite being considered unfeasible (A: 84.13%; F:67.20%) in clinical practice. Agreement was reached on using ACT, TAI, mMRC, and a dispensing register every three months; mini-AQLQ and MMAS every six months; and EQ-5D every twelve months. CONCLUSION: This consensus paves the way toward patient-centered care, promoting the development of strategies supporting routine assessment of PROs in severe asthma management.

Buccopharyngeal route administered high polyphenolic olive oil and COVID-19: A pilot clinical trial.

INTRODUCTION: Waning immunity after vaccination justifies the need for additional effective COVID-19 treatments. Immunomodulation of local immune response at the oropharyngeal mucosa could hypothetically activate mucosal immunity, which can prevent SARS-CoV-2 main immune evasion mechanisms in early stages of the disease and send an effective warning to other components of immune system. Olive polyphenols are biologically active compounds with immunomodulatory activity. There are previous studies based on immunomodulation with olive polyphenols and respiratory infections using an enteral route, which point to potential effects on time to resolution of symptoms. The investigators sought to determine whether participants following immunomodulation with tiny quantities of high polyphenolic olive oil administered through an oromucosal route could have a better outcome in COVID-19. SUMMARY: This pilot clinical trial investigated the effect of buccopharyngeal administered high polyphenolic olive oil on COVID-19 incidence, duration, and severity. IMPORTANCE: Waning immunity after vaccination justifies the need of further research for additional effective treatments for COVID-19. OBJECTIVE: Immunomodulation of local immune response at the buccopharyngeal mucosa could hypothetically activate mucosal immunity, which would in turn difficult SARS-CoV-2 immune evasion mechanisms in early stages of the disease and send an effective warning to other components of immune system. Olive polyphenols are biologically active compounds with immunomodulatory activity. There are previous studies based on immunomodulation with olive polyphenols and respiratory infections, using an enteral route, which suggest potential shortening of time to resolution of symptoms. The investigators sought to determine whether participants following immunomodulation with tiny quantities of high polyphenolic olive oil administered through an oromucosal route could have a better outcome in COVID-19. DESIGN, SETTING, AND PARTICIPANTS: Double blind, randomized pilot clinical trial conducted at a single site, Talavera de la Reina, Spain. Potential study participants were identified by simple random sampling from the epidemiological database of contact patients recently diagnosed of COVID-19 during the study period. A total of 88 adult participants were enrolled and 84 completed the 3-month study, conducted between July 1, 2021 and August 31, 2022. INTERVENTION: Participants were randomized to receive oromucosal administered high polyphenolic olive oil, 2 mL twice a day for 3 months or no treatment. MAIN OUTCOME AND MEASURES: Primary outcomes were incidence, duration, and severity of COVID-19 after intervention. RESULTS: There were no differences in incidence between both groups but there were significant differences in duration, the median time to resolution of symptoms was 3 days in the high polyphenolic olive oil group compared with 7 days in the no-treatment group. Although time to resolution is directly related to severity, this study did not find any differences in severity. CONCLUSION AND RELEVANCE: Among full-vaccinated adults recent infected with COVID-19, a daily intake of tiny quantities of oromucosal administered high polyphenolic olive oil before infection significantly improved the time to symptom resolution. This finding strongly support the appropriateness of further deep research on the use of oromucosal administered high polyphenolic olive oil as an effective immune strategy against COVID-19.

Role of Dau c 1 in three different patterns of carrot-induced asthma.

OBJECTIVE: To assess the role of Dau c 1 in three patients with carrot induced asthma. MATERIAL AND METHODS: Patient 1 had asthma when handling raw carrots. Sensitization to pollens wasn't detected. Patient 2 had rhinoconjunctivitis due to grass and olive pollen allergy. She had asthma when handling raw carrots. Patient 3 was diagnosed of rhinoconjunctivitis and asthma due to allergic sensitization to mites, several pollens and cat. She had asthma due to raw carrot ingestion and inhalation. IgE immunobot analysis and ELISA inhibition assay were used to investigate the allergens and specific antibodies. RESULTS: IgE Immunoblot Analysis: Dau c 1 from carrot extract and the recombinant rDau c 1 were recognized by IgE from patients 1 and 2. Band of Bet v 1 in birch pollen extract wasn't recognized. Patient 3 didn't recognize any of these allergens. Specific IgE to rDau c 1 was measured by ELISA. Specific IgE ELISA-inhibition with carrot as solid phase showed an intermediate inhibition (30 %) between carrot and rDau c 1 in patient 1; and a considerable inhibition (nearly 100 %) between carrot and rDau c 1 in patient 2. No inhibition was found in patient 3. Specific IgE ELISA inhibition between rDau c 1 and rBet v 1, employing rDau c 1 as solid phase was made in patients 1 and 2. Bet v 1 showed less than 40 % of inhibition of rDau c 1 in patient 1; and an intermediate inhibition (> 40 %) between rBet v 1 and rDau c 1 in patient 2. CONCLUSIONS: Airborne carrot allergens are able to sensitize without the implication of a previous pollen allergy. Dau c 1 was the main allergen in patient 2. In patient 1, there was a band of 30 kd that looks like the predominant allergen. Patients 1 and 2 were sensitized directly from carrot allergens. In patient 3, Dau c 1 isn't related to the carrot allergy. Allergy to carrot in patient 3 seems to be related to her allergy to different pollens; however, it wasn't related to birch pollen. Mediterranean countries didn't show the same patterns of food-related pollen allergy than Nordic countries.

Lupine inhalation induced asthma in a child.

The ingestion of lupine seed flour has been reported as a cause of allergic reactions. There is some evidence of its allergenic potential after inhalation. An 8-year-old asthmatic child, who was allergic to peanut, was studied in our clinic with the suspicion of an adverse drug reaction due to salbutamol. He suffered an asthma attack while playing with his brother, who had been eating lupine seed as snack; surprisingly, the asthma attack worsened with salbutamol. The skin tests showed a positive result with Lupinus albus extract, peanut, garbanzo bean, navy bean, pea, green bean, lentil, soy, Olea europea pollen, grass pollen and Plantago lanceolata pollen. The prick-by-prick tests both from dried seeds and those preserved in salt and water were strongly positive. Serum specific IgE antibodies were positive to Lupine albus (1.43 kU/l), peanut (4.32 kU/l), soy (2.15 kU/l), lentil (3.12 kU/l) and garbanzo (0.7 kU/l). After informed consent salbutamol was well tolerated but the patient had asthma in 5 min of manipulation of the lupine seeds. In our case, reactivity with other legumes was also demonstrated, but only peanut allergy was relevant because boiled legumes were tolerated. It is also notorious that anamnesis is so important to assess the true etiological agents of asthma.

Allergy to banana in a 5-month-old infant.

Food proteins can sensitize the infants via different sources. A 5-month-old boy suffered three episodes of generalized urticaria 20 min after the ingestion of a fruit purée containing apple, banana and orange. Skin testing showed positive results to banana and chestnut. Other tests were negative. The value of specific immunoglobulin E (Pharmacia CAP-FEIA, Uppsala, Sweden) to banana was 58 KU/l, to orange was 9.7 KU/l, to chestnut was 5.6 KU/l and to latex was 1.6 KU/l. Orange, apple and latex products were well tolerated. He never had eaten chestnut. The parents rejected a banana challenge test. The route of sensitization in our case might be via placenta, breast-milk, and inadvertent oral intake of food or even via inhalation. An early frequent exposure to banana allergens was considered a possibility factor for the development of banana sensitization. We found that the banana consumption during pregnancy and lactation by the mother of our patient was greater than usual. It is not frequent to find so high levels of sensitization to any fruit in first year of life. In our case, latex, chestnut and orange sensitizations did not seem to be clinically relevant. However, latex and foods known to cross-react with banana antigens should be given to banana-sensitive individuals with great caution.

Anisakis simplex only provokes allergic symptoms when the worm parasitises the gastrointestinal tract.

We analysed patients with allergic or digestive symptoms after seafood ingestion in order to assess a correct diet in Anisakis simplex sensitised individuals. A total of 120 patients who suffered allergic and/or digestive symptoms after marine food ingestion were studied. We performed skin prick tests for A. simplex and seafood, total serum and specific serum immunoglobulin E to A. simplex in the acute stage and 1 month later. A gastroscopy was carried out to find larvae in those patients with persistent abdominal pain. A challenge with non-infective larvae was performed to assess a correct diet. Some 96 patients were sensitised to A. simplex. Gastroscopy was performed in 47 and we detected larvae in 24. We compared symptoms, skin tests, total and specific IgE and the latency of appearance of symptoms in patients positive for Anisakis larvae, patients without larvae at gastroscopy and patients without digestive symptoms. There was no difference among the groups. We challenged 22 patients with frozen A. simplex larvae. After allowing deep-frozen seafood in the diet for more than 2 years, no patient suffered a reaction. At this time, we allowed all our patients well-frozen seafood without any allergic reaction occurring. Allergic symptoms are the most frequent manifestation of A. simplex parasitism. We could not find any patient allergic to the thermostable proteins of parasite.