A recent study identified the basophil activation test as the most accurate test in predicting 

 to baked and fresh cow’s milk during oral food challenges, compared with skin prick testing and IgE testing.

“Even if sometimes the difference in diagnostic accuracy of [basophil activation tests] and other tests was relatively small, we consider that every additional patient diagnosed correctly is clinically relevant,” wrote study investigator Irene Bartha, PhD, from department of women and children's health (Pediatric Allergy) at King's College London, and colleagues.

Cow’s milk allergy has an estimated worldwide prevalence of 5.7%.

 Research has shown that tolerating baked milk is associated with improved cow’s milk allergy outcomes and quality of life, but current tests—skin prick tests and specific IgE (sIgE)—cannot accurately identify children who can tolerate baked milk without doing an oral food challenge.

 In this study, investigators compared the diagnostic performance of the basophil activation test, the skin prick test, and the specific IgE during fresh milk oral food challenges.

The team recruited children aged 6 months to 15 years who visited various specialized pediatric allergy clinics in London. Children were eligible if they either had a history of an immediate-type allergic reaction to cow’s milk, no history of cow’s milk consumption, or evidence of IgE sensitization as documented by SPT or serum sIgE. Investigators excluded children with significant chronic illness outside of atopic disease, history of severe life-threatening food reactions, inability to undergo a diagnostic food challenge, recent or ongoing systemic immunosuppressive treatments, current use of omalizumab or food allergen immunotherapy, and inability to discontinue antihistamines before skin prick testing.

Skin prick testing involved cow’s milk extract, fresh milk, and baked milk slurry (prepared the day of the challenge with 1 g of the challenge food in 10 mL of saline), and a single-headed metal lancet. Investigators used 10 mg/mL histamine dihydrochloride and 50% glycerol in buffered saline as positive and negative controls, respectively.

IgE testing measured total IgE or sIgE levels to cow’s milk, boiled milk, alpha-lactalbumin, beta-lactoglobulin, and casein.

Lastly, basophil activation testing, conducted by the Santos Lab at King’s College London, used whole blood incubated with milk extract, baked milk, anti-IgE, formyl-methionyl-leucyl-phenylalanine, or controls, followed by staining, flow cytometry, and analysis of basophil activation (%CD63+ and SI CD203c), with non-responders defined as <5% CD63+ basophils to anti-IgE and allergen.

All children aged ≥ 12 months had a double-blind, placebo-controlled food challenge, and those under 12 years had an open incremental oral food challenge. Among 150 children given a baked milk challenge, 85% tolerated it and proceeded to a fresh milk challenge, of which 56% passed.

Overall, the basophil activation test demonstrated the best accuracy at predicting allergic reactions to both baked and fresh milk, with an area under the receiver operator characteristic curve of 0.90 and 0.81, respectively, compared with sIgE (0.75 and 0.74) and a skin prick test (0.70 and 0.78).

Using cut-offs with 100% sensitivity and specificity, the proportion of children who would undergo a baked milk oral food challenge would be 99% for skin prick testing to baked milk, 82% for SIgE to boiled milk, and 49% for basophil activation test to baked milk. Among those tested, the proportion with a positive result would be 13% for the skin prick test, 17% for sIgE, and 24% for the basophil activation test. This shows that the basophil activation test selects fewer children for testing but identifies a greater percentage of true positives.

Among children under 2 years, only 27% required an oral food challenge following a basophil activation test to baked milk, compared with 100% following a skin prick test and 81% following sIgE to milk extract. The analysis showed that this finding had 100% diagnostic accuracy.

“Whether [basophil activation test] brings additional value to existing tests is a wider question that needs to consider other factors, such as availability of tests, access and capacity to do [oral food challenge], acceptable risk and patient preferences,” investigators wrote.

 “Interestingly, the second-best test was different for [baked milk] allergy and for [fresh milk] allergy. For BM allergy, sIgE was better than SPT. For FM allergy, it was the reverse.”

Bartha I, Boyd H, Foong RX, et al. The Basophil Activation Test Is the Most Accurate Test in Predicting Allergic Reactions to Baked and Fresh Cow's Milk During Oral Food Challenges. 

. Published online August 13, 2025. doi:10.1111/all.16675

Spolidoro GCI, Ali MM, Amera YT, et al. Prevalence estimates of eight big food allergies in Europe: Updated systematic review and meta-analysis. 

. 2023;78(9):2361-2417. doi:10.1111/all.15801

Articles

A study has identified the basophil activation test as the most accurate method for predicting allergic reactions to both baked and fresh cow's milk during oral food challenges. This test outperformed skin prick and specific IgE tests, showing higher diagnostic accuracy. The study involved children aged 6 months to 15 years, with specific inclusion and exclusion criteria. The basophil activation test demonstrated superior accuracy, particularly in selecting fewer children for testing while identifying a higher percentage of true positives. The study suggests further evaluation of the test's value considering factors like availability and patient preferences.

The basophil activation test shows the greatest accuracy in predicting allergic reactions to baked and fresh cow’s milk, reducing the need for oral food challenges in children.

Basophil Activation Test Outperforms SPT and IgE in Milk Allergy Challenge

As part of Psoriasis Action Month, patient narratives reveal the complex interplay between disease severity, comorbidities, and psychosocial burden in psoriasis management. Cases like those of Ayesha Patrick, Brian Lehrschall, and Janene Tirado illustrate the heterogeneity of psoriasis, spanning common chronic plaque forms, rare pustular variants, and the compounded impact of multimorbidity. These stories underscore the importance of timely diagnosis, culturally competent care, and multidisciplinary management in optimizing outcomes.

Lessons from Psoriasis Action Month: Insights from Three Patient Journeys

Ayesha Patrick’s journey underscores the challenges and gaps in care for women of color with psoriasis. Ayesha lived with symptoms for much of her life without a formal diagnosis. Early manifestations, including flaking scalp and dry skin, were misattributed to “winter itch” or dandruff. It was not until college that she was formally diagnosed with psoriasis. Initially mild, her disease escalated during the COVID-19 pandemic, presenting simultaneously as plaque, guttate, and inverse psoriasis.

Virtual care during this period posed unique challenges. Ayesha recalls feeling vulnerable exposing her skin over video visits, particularly with severe scalp involvement characterized by relentless flaking and inflammation. This acute flare highlighted the systemic and psychosocial impact of psoriasis and emphasized the importance of timely, patient-centered care.

Ayesha’s experience highlights several critical clinical considerations. Psoriasis often presents differently in patients with darker skin tones, appearing purplish or gray rather than red, yet educational resources and clinical training frequently underrepresent these variations. This knowledge gap contributes to delayed diagnosis and mismanagement. Additionally, standard treatment regimens may not account for hair texture or cultural hair care practices, as illustrated by Ayesha’s experience with a daily medicated shampoo that caused hair loss.

Her advocacy led to the creation of Sistas with Psoriasis (now The PsoriaSis Collective), emphasizing culturally informed support, education, and access to reliable resources. Ayesha’s story underscores the need for clinicians to actively validate patient concerns, provide individualized treatment strategies, and recognize how disease presentation may vary across populations.

Key takeaways for practice include early recognition, culturally competent patient education, consideration of hair care practices in treatment planning, and the importance of connecting patients with advocacy networks. Clinicians are encouraged to ensure that their diagnostic approach and management strategies reflect the diverse presentations of psoriasis, particularly in patients of color.

Patient stories can provide important insights into the complexities of multimorbidity. One such example is Brian Lehrschall, diagnosed with psoriasis at age 13, who rapidly progressed to near–total body surface area involvement. Over time, he also developed psoriatic arthritis, with pain and stiffness limiting physical activity. Biologic therapies reduced his skin involvement to approximately 25% body surface area (BSA), but he continued to live with persistent disease burden.

Reduced activity contributed to weight gain and, ultimately, the development of type 2 diabetes. His diabetes was first identified during an acute episode of severe hyperglycemia (blood glucose >800 mg/dL). Initial management with metformin was insufficient, prompting escalation to a glucagon-like peptide-1 (GLP-1) receptor agonist. This intervention produced substantial weight loss (initially approximately 30 pounds, later exceeding 100 pounds with a switch to another GLP-1 agent).

Notably, weight reduction yielded dual benefits: improved glycemic control and an unanticipated improvement in psoriatic arthritis symptoms, with reduced hip, knee, and back pain. These changes facilitated increased mobility and physical activity, which further supported weight management and enhanced quality of life.

Brian’s case underscores several clinical considerations:

 Psoriasis and psoriatic arthritis frequently coexist with cardiometabolic disease, creating complex management needs.

 Beyond glycemic and weight outcomes, patients may experience musculoskeletal and inflammatory improvements that positively affect arthritis symptoms.

 Optimal outcomes required input from dermatology, rheumatology, and endocrinology, reinforcing the importance of a multidisciplinary approach.

This case highlights the potential for GLP-1 therapy to improve outcomes across multiple domains in patients with overlapping chronic conditions. It also demonstrates the value of encouraging incremental physical activity and shared decision-making to enhance adherence and patient engagement.

Janene Tirado’s experience with generalized pustular psoriasis (GPP) and palmoplantar pustulosis (PPP) highlights the diagnostic and management challenges associated with rare psoriasis subtypes. Her journey illustrates the potential severity of these conditions and the critical importance of timely, accurate diagnosis.

Janene first noticed atypical blisters on her foot during a golf tournament, initially presumed to be an allergic reaction. Within hours, lesions rapidly progressed bilaterally, accompanied by fever and impaired mobility. She initially presented to an emergency department where she was misdiagnosed with tinea pedis and discharged with topical antifungals. Overnight, her condition worsened, with extensive pustular eruptions, incapacitating pain, and systemic symptoms.

When she eventually accessed dermatologic care, she was diagnosed with GPP—a rare, potentially life-threatening psoriasis variant requiring specialized management. Her case emphasizes the need for clinicians to maintain a high index of suspicion for pustular forms of psoriasis, particularly when rapid lesion progression and systemic symptoms occur. Early recognition and intervention are essential to mitigate complications and improve outcomes.

Janene’s post-flare course has been marked by residual scarring, ongoing sensitivity, and functional limitations, underscoring the long-term impact of GPP/PPP on quality of life. Her experience also highlights the psychosocial burden associated with delayed diagnosis and mismanagement.

Her story reinforces several key considerations: the importance of patient-centered evaluation when common diagnoses fail to align with clinical presentation, awareness of rare psoriasis phenotypes, and early referral to dermatology specialists. Supporting patients through education, anticipatory guidance, and evidence-based therapy can improve both clinical outcomes and patient resilience in managing rare psoriasis subtypes.

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Multidisciplinary management and patient-centered care are critical for optimizing outcomes in complex or severe psoriasis cases.

Welcome back to our recap of this month's news and updates from the 

In August 2025, the FDA issued a series of landmark decisions spanning neurology, pulmonology, rare diseases, pain, and metabolic health. Highlights included the first approval of a CGRP antagonist for pediatric migraine prevention with fremanezumab, new authorizations for PharmaTher’s ketamine in surgical pain and Tonix’s TNX-102 SL as the first fibromyalgia therapy in over 15 years, and the historic approval of brensocatib as the first disease-modifying treatment for bronchiectasis. Additional milestones featured the first immunotherapy for recurrent respiratory papillomatosis with zopapogene imadenovec, semaglutide’s expansion into metabolic dysfunction-associated steatohepatitis with fibrosis, and Ionis’ donidalorsen to prevent hereditary angioedema attacks. The month also closed with a setback, as Outlook Therapeutics received a Complete Response Letter for ONS-5010 in wet AMD, due to a trial's failure to meet its primary endpoint. Here’s a concise overview of the key FDA decisions and updates from August 2025.

Want to hear from the experts? Look for our Related Content links underneath blurbs for insight into how this decision might influence practice moving forward.

FDA Approves Fremanezumab to Prevent Episodic Migraine in Children

On August 6, 2025, Teva Pharmaceuticals announced FDA approval of fremanezumab (AJOVY) for the preventive treatment of episodic migraine in children and adolescents aged 6–17 years weighing at least 99 pounds. Based on phase 3 SPACE trial results, the therapy significantly reduced monthly migraine and headache days versus placebo and demonstrated a consistent safety profile in pediatric patients compared with adults. This marks the first approval of a CGRP antagonist for pediatric episodic migraine prevention, expanding fremanezumab’s prior adult indication. The treatment is available as a once-monthly injection, with common adverse events including injection site reactions.

FDA Approves PharmaTher’s Ketamine for Surgical Pain Management

On August 8, 2025, PharmaTher announced FDA approval of ketamine (KetaRx) for surgical pain management. Based on resolution of prior complete response letters that required clarification of manufacturing and product details without new clinical trials, the approval provides an additional option amid ongoing ketamine shortages. The dissociative anesthetic, long included on the WHO Model List of Essential Medicines, is expected to support perioperative pain care while also laying groundwork for potential future indications in psychiatry, neurology, and chronic pain. PharmaTher noted the approval positions the company to expand its ketamine-based pharmaceutical portfolio globally.

FDA Approves First Bronchiectasis Therapy, Brensocatib, for Ages 12 and Up

On August 12, 2025, the FDA approved brensocatib (Brinsupri) 10 mg and 25 mg for adults and adolescents with non-cystic fibrosis bronchiectasis, marking the first disease-modifying therapy for this condition. The approval was supported by results from the phase 3 ASPEN trial, which demonstrated significant reductions in pulmonary exacerbation rates over 52 weeks compared with placebo. Nearly half of patients receiving brensocatib remained exacerbation-free at one year, and improvements in lung function were observed, particularly with the higher dose. Safety findings were generally consistent across groups, with hyperkeratosis noted more often in treated patients. 

Zopapogene Imadenovec First Immunotherapy Approved for Recurrent Respiratory Papillomatosis

On August 14, 2025, the FDA approved zopapogene imadenovec-drba (Papzimeos) as the first non-replicating adenoviral vector-based immunotherapy for adults with recurrent respiratory papillomatosis (RRP). The decision, supported by pivotal phase 1/2 trial data showing a 51% complete response rate and durable reductions in surgical burden, represents a transformative step for a rare HPV-driven disease long managed primarily through repeated surgeries. With a favorable safety profile and meaningful clinical benefit, the therapy introduces a novel immunotherapy option that directly addresses the cycle of recurrence and morbidity in RRP.

FDA Approves TNX-102 SL, First New Fibromyalgia Therapy in 15 Years

On August 15, 2025, the FDA approved Tonix Pharmaceuticals’ TNX-102 SL (Tonmya) for the treatment of adults with fibromyalgia, marking the first new drug for the condition in more than 15 years. The sublingual cyclobenzaprine formulation, also the first in a new class of non-opioid analgesics for fibromyalgia, demonstrated significant reductions in daily pain scores and improvements in sleep, fatigue, and quality of life measures in the phase 3 RESILIENT trial. With a tolerable safety profile and rapid onset of effect, Tonmya introduces a novel therapeutic option for a patient population with historically limited treatment choices.

FDA Approves Semaglutide (Wegovy) Injection 2.4 mg for Noncirrhotic MASH

On August 15, 2025, the FDA approved Novo Nordisk’s semaglutide (Wegovy) 2.4 mg injection for adults with metabolic dysfunction-associated steatohepatitis (MASH) with moderate to advanced fibrosis, making it the first GLP-1 receptor agonist authorized for this indication. The approval was supported by phase 3 ESSENCE trial results, in which semaglutide significantly improved liver histology, with 63% of patients achieving resolution of steatohepatitis without worsening fibrosis and 37% showing fibrosis improvement without worsening steatohepatitis at 72 weeks.

FDA Approves Donidalorsen to Prevent Hereditary Angioedema Attacks

On August 21, 2025, the FDA approved Ionis Pharmaceuticals’ donidalorsen (DAWNZERA), an RNA-targeted therapy to prevent hereditary angioedema (HAE) attacks in patients 12 years and older. Backed by pivotal OASIS-HAE and OASISplus phase 3 trials and long-term extension data, donidalorsen reduced monthly attacks by an average of 81% versus placebo. Patients switching from existing prophylactic treatments also saw further attack-rate reductions, and the therapy was well tolerated, with mostly mild injection site reactions. 

FDA Issues CRL to Outlook Therapeutics' ONS-5010 for the Treatment of Wet AMD

On August 29, 2025, Outlook Therapeutics announced it had received a Complete Response Letter (CRL) from the FDA for its Biologics License Application for ONS-5010 (LYTENAVA), an ophthalmic formulation of bevacizumab in development for wet age-related macular degeneration (AMD). The agency cited the phase 3 NORSE EIGHT trial’s failure to meet its primary efficacy endpoint, noting insufficient evidence of effectiveness despite prior success in the NORSE TWO study. 

July and August 2025 saw significant FDA advancements, with approvals across various therapeutic areas, including the first oral treatment for hereditary angioedema and the first therapy for C3 glomerulopathy. Notable approvals included fremanezumab for pediatric migraine prevention, ketamine for surgical pain, and brensocatib for bronchiectasis. Zopapogene imadenovec emerged as the first immunotherapy for recurrent respiratory papillomatosis, while TNX-102 SL was approved for fibromyalgia. Semaglutide received approval for noncirrhotic MASH, and donidalorsen for hereditary angioedema prevention. However, a CRL was issued for ONS-5010 for wet AMD.

This FDA News Month in Review provides a round-up of regulatory decisions from August 2025.

8 FDA Headlines You Missed in August 2025

New research is shedding light on the potential benefit of a remotely delivered, positive psychological-based gut-brain behavior therapy for improving 

The intervention, coined Well-being in IBS: Strengths and Happiness (WISH), is a novel, 9-week, manualized, phone-delivered, IBS-specific positive psychological intervention to promote greater positive psychological wellbeing and improved health-related quality of life (HRQoL) and IBS symptoms. Findings from this proof-of-concept trial highlight its feasibility, acceptability, and early benefits for IBS symptom severity, IBS HRQoL, depression, GI symptom-specific anxiety, pain catastrophizing, avoidant/restrictive eating behaviors, physical activity engagement, and resilience.

Classified as a disorder of gut–brain interaction, IBS is thought to arise from complex interactions between biological, psychological, and social factors. Existing treatments focus primarily on alleviating symptoms rather than achieving cure. Brain–gut behavior therapies may offer a promising treatment option for IBS, but current approaches do not benefit all patients.

“Interventions to boost positive psychological wellbeing in IBS have not yet been investigated and represent a much needed area of future research,” Elizabeth Madva, MD, an associate program director for the residency at the Massachusetts General Hospital site and a co-director of the residency’s Clinician Educator Program, and colleagues wrote.

To address this, investigators developed WISH, a 9-week remote intervention that aims to improve IBS symptoms by specifically targeting the promotion of greater positive psychological wellbeing. It consists of 9 weekly positive psychological exercises focused on cultivating gratitude, personal strengths, and sense of purpose/meaning, which were completed independently and later reviewed in weekly phone sessions with a study interventionist.

In the present randomized waitlist-controlled proof-of-concept trial, investigators sought to examine WISH's feasibility, acceptability, and preliminary effects on key psychological and IBS-related outcomes.

Adult participants ≥ 18 years of age with a diagnosis of IBS meeting Rome IV criteria were recruited from an urban academic medical center between March and December 2022 via GI clinician referral and the institution's research patient data registry. Exclusion criteria included limited English proficiency, lack of telephone access, cognitive deficits limiting participation, and current manic episode, psychosis, or active substance use disorder that would limit participation.

A total of 22 eligible adults were randomized, stratified by gender and IBS subtype, to the intervention (n = 12) or waitlist-control (n = 10) groups. After waiting for 9 weeks with continued treatment as usual, waitlist-control participants repeated a second set of baseline self-report measures and then completed the WISH intervention.

The primary outcome was feasibility, assessed by the proportion of total positive psychological exercises and associated phone sessions completed. Acceptability was assessed with weekly ratings of ease and utility of each exercise on 10-point Likert scales.

Among the study cohort, the mean age was 50.6 (range 19 to 79) years, 55% (n = 12) were female, and most identified as White (86%; n = 19). Of the 22 randomized participants, 18 (82%) completed 100% of the intervention, and 85% of all exercises were completed across participants, which investigators noted was above their a priori feasibility thresholds of 70% and 65%, respectively.

Of note, the WISH sessions also met investigators’ a priori acceptability threshold, with mean ease scores of 7.2 (95% CI, 6.70 to 7.75) and utility scores of 7.6 (95% CI, 7.14 to 8.01) on 0–10 Likert scales, respectively.

On average, each positive psychological exercise led to a 1.22-point increase in happiness (6.05 pre-intervention; Standard deviation [SD], 1.77 vs 7.28 post-intervention; SD, 1.60; 

 <.001) and a 1.05-point increase in optimism (6.20 pre-invervention; SD, 1.84 vs 7.24 post-intervention; SD, 1.68; 

Compared to the waitlist-control group, the WISH intervention resulted in modestly greater improvements in key psychological outcomes including resilience (B = 0.30; 

 = 0.39), depression (B = −1.50; 

 = −0.43), GI symptom-specific anxiety (B = −6.67; 

 = −0.36), and pain catastrophizing (B = −3.26; 

 = −0.32). Notably, WISH also achieved greater improvements in IBS symptom severity (B = −23.20; 

 = −0.20), IBS HRQoL (B = 2.67; 

 = 0.12), avoidant/restrictive eating behaviors (B = −7.48; 

 = −0.69), and physical activity engagement (B = 396.70; 

Of the 18 participants who completed the WISH intervention across both groups, 11 (61%) no longer met Rome IV criteria for IBS after program completion (95% CI, 0.36 to 0.83).

“WISH's effects will subsequently need to be confirmed in a larger, randomized controlled trial powered to detect between-group differences in outcomes,” investigators concluded.

 “If effective, WISH has the potential to improve key IBS-related outcomes and to fill a critical care gap for this chronic, high comorbidity condition associated with substantial healthcare costs, impaired function, and reduced quality of life.”

Madva EN, Huffman JC, Castillo C, et al. A Randomized Waitlist-Controlled Trial of a Positive Psychology Intervention for Irritable Bowel Syndrome: The WISH Proof-of-Concept Trial. 

American College of Gastroenterology. Irritable Bowel Syndrome. Accessed August 29, 2025. 

https://gi.org/topics/irritable-bowel-syndrome/

A novel intervention, Well-being in IBS: Strengths and Happiness (WISH), shows promise in improving psychological and IBS-related outcomes through a 9-week, phone-delivered positive psychological therapy. This proof-of-concept trial demonstrated the feasibility and acceptability of WISH, with significant improvements in IBS symptom severity, health-related quality of life, depression, anxiety, and resilience. The study involved 22 adults with IBS, and 61% of participants no longer met Rome IV criteria for IBS post-intervention. Further research is needed to confirm these findings in larger, randomized controlled trials.

The 9-week intervention targeting positive psychological wellbeing in IBS was feasible, well-accepted, and linked to improvements in IBS-related outcomes.

Positive Psychological Gut-Brain Behavior Therapy Shows Early Benefit for IBS

New research found that combining oral microbiome and inflammatory mediator data with clinical history provides a more accurate way to identify children at risk of future severe asthma attacks.

Children with persistent asthma who experienced ≥ 1 severe attack in the previous year have a 2- to 2.5-fold higher risk of future severe attacks, according to earlier studies.

 Detecting which children are at risk for asthma attacks early on can help clinicians tailor and optimize management.

Investigators sought to develop a prediction model for future asthma attacks in children that encompasses both epidemiological and clinical data, along with objective biomarkers.

 In their predictive model, the team aimed to incorporate salivary microbiome and serum inflammatory mediator profiles with asthma attack history. They assessed the model during a discovery (SysPharmPediA) and a replication (U-BIOPRED) phase.

“This approach aligns with current recommendations that predictive models of severe asthma attacks should include a combination of epidemiological/clinical data, as well as objective biomarkers,” wrote study investigator Shahriyar Shahbazi Khamas, PharmD, PhD candidate, from Amsterdam University Medical Center in the Netherlands, and colleagues.

Investigators classified the 154 children, 121 in the SysPharmPediA phase and 33 in the U-BIOPRED phase, into at-risk and no-risk groups.

 The presence or absence of ≥ 1 severe attack over the 1-year follow-up served as the basis for classification. Children were between the ages of 6 and 17 years and were mostly Caucasian (SysPharmPediA: at risk (77.1%), no risk (49.1%); U-BIOPRED: at risk (88.9%), no risk (50%) and female SysPharmPediA: at risk (60%), no risk (30.9%); U-BIOPRED: at risk (59.3%), no risk (66.7%).

Using a random forest approach, the team trained prediction models on 70% of the dataset, incorporating past attack history, microbiome composition, and serum inflammatory mediators. Investigators then tested the models on the remaining 30% of the population.

During the discovery phase, the model trained on past asthma attacks yielded an area under the receiver operating characteristic curve (AUROCC) of about 0.7. Models trained on 6 salivary bacteria or 6 inflammatory mediators achieved similar findings. However, models trained with all 7 features—past asthma attacks, 

, TIMP-4, VEGF, and MIP-3β—achieved the greatest accuracy with an AUROCC of ~0.87.

“This model showed a substantial improvement in predictive accuracy compared to the individual models; meaning it might better inform physicians when assessing the risk of future asthma attacks in a child, potentially enabling more informed clinical decisions regarding preventive intervention,” investigators wrote.

In the replication phase, they could not include all the markers from the original model because only 1 inflammatory mediator, VEGF, was available. Still, the combined model with data on VEGF, past asthma attack history, and the 3 salivary bacteria (

) achieved an AUROCC of 0.84. This showed that the combined model had a strong predictive accuracy for future asthma attacks, even without the other inflammatory mediators.

Investigators found that, apart from Capnocytophaga, all other predictive bacteria were more prevalent in children who remained attack-free during follow-up. These findings align with earlier research reporting greater sputum levels of Capnocytophaga in children experiencing asthma attacks, with a positive correlation to MIP-1β, a key eosinophil-recruiting mediator.

The final predictive model included three key serum mediators—TIMP-4, VEGF, and MIP-3β—which collectively drive inflammation, immune activation, and airway remodeling. Their interplay may create a cycle of inflammation and structural change that heightens the risk of severe asthma attacks.

—including lipopolysaccharides, short-chain fatty acids, hydrogen sulfide, and ammonia—may drive airway inflammation and remodeling by affecting VEGF, MMP/TIMP-4 balance, and MIP-3β–mediated immune responses. These pathways likely contribute to asthma progression and merit further investigation.

“The integration of salivary bacterial composition and inflammatory profiles in serum showed promise for improving predictive accuracy and may offer insights into the mechanisms underlying asthma attacks,” investigators concluded.

“Compared to conventional biomarkers like FENO and blood eosinophil count, which showed poor predictive performance in this study, the combined model demonstrated superior predictive capability… Notably, while a history of past asthma attacks emerged as a strong individual predictor…our results show that incorporating microbiome and inflammatory mediator data significantly enhances model performance.”

Shahbazi Khamas S, Brinkman P, Neerincx AH, et al. Complementary Predictors for Asthma Attack Prediction in Children: Salivary Microbiome, Serum Inflammatory Mediators, and Past Attack History. 

. Published online August 18, 2025. doi:10.1111/all.70004

Covar RA, Szefler SJ, Zeiger RS, et al. Factors associated with asthma exacerbations during a long-term clinical trial of controller medications in children. 

. 2008;122(4):741-747.e4. doi:10.1016/j.jaci.2008.08.021

Combining oral microbiome and inflammatory mediator data with clinical history enhances the prediction of severe asthma attacks in children. A new model incorporating salivary microbiome and serum inflammatory mediator profiles, alongside asthma attack history, demonstrated improved predictive accuracy. The model, tested in two phases, achieved an AUROCC of ~0.87, outperforming individual models. Key components included past attack history, specific bacteria, and serum mediators. This approach may inform clinical decisions and preventive interventions, offering insights into asthma mechanisms and surpassing conventional biomarkers like FENO and blood eosinophil count.

Combining salivary bacteria, serum markers, and past attack history improves risk prediction for severe asthma attacks in children.

Oral Microbiome, Serum Markers Improve Childhood Asthma Risk Prediction

A recently developed artificial intelligence (AI) model known as YOLO v5 is effective in classifying 

 following patch tests, new data suggest, allowing for swift and accurate evaluations.

The data regarding this new AI model for classification of skin erythema from patch tests were authored by investigators such as Seoyoung Kim, from the Department of Integrative Biotechnology at Sungkyunkwan University in South Korea. Kim et al noted that recent studies have examined AI’s implementation as an assistive diagnostic tool in dermatology.

Advances in machine learning (ML) and deep learning (DL) have also led to certain studies highlighting the feasibility of utilizing ML to automate skin reaction detection.

“These investigations highlight the revolutionary potential of AI-powered diagnostics in dermatology, particularly for improving the accuracy, consistency and accessibility of epicutaneous patch testing,” Kim and coauthors wrote.

 “In this study, we developed a model that overcomes the limitations of the convolutional neural network (CNN) to classify skin irritation from images using the object detection algorithm YOLO v5 (You Only Looking Once version 5).”

The investigative team gathered patch test data from trial participants between 2020 - 2023, assessing patients who had been recruited in Seoul and the Gyeonggi Province who had also voluntarily enrolled in their analysis. Individuals deemed eligible for enrollment in the trial were adults ≥18 years who were shown to have healthy skin and were able to provide written informed consent and commit to follow-up visits as well as all other study requirements.

The patch testing required for Kim and colleagues' research was carried out using Van der Bend chambers, which consisted of hypoallergenic, medical-grade non-woven polyester and contained chromatographic filter paper. The investigators would apply cosmetics or cosmetic ingredients to the upper back of study subjects and leave these in place for 24 hours. Participants' skin responses were then evaluated 1 hour and 24 hours after removal. Reactions were graded on a 5-point scale and were adapted from the Frosch and Kligman method and CTFA safety guidelines:

1: Mild erythema, either scattered or diffuse

4: Pronounced erythema with edema and vesicles

The team, for the purposes of documenting responses, gathered standardized clinical photographs under controlled conditions, regardless of whether a reaction occurred. All images were captured by Kim and colleagues at a fixed resolution of 4160 × 2768 pixels to allow for the detection of any subtle erythematous shifts. Preprocessing of images was performed to prepare them for analysis with the YOLOv5x deep learning algorithm.

Each of the collected images was assessed independently by 4 evaluators. In cases of discordance, the investigators instructed a senior reviewer to provide the final score. Annotations were later mapped to corresponding bounding boxes within the dataset.

Kim and coauthors' training dataset was made up of 83,629 images, with 1,312 and 1,536 images being utilized for evaluation and validation, respectively. Overall, the AI model attained a classification accuracy of 0.983 at both the 24 and 48-hour mark.

 The model's F1 score, indicating a balance between precision and recall, was shown to be 0.982.

In terms of individual grades, the areas under the curve (AUCs) were shown to be 0.914 for score 0, 0.838 for score 1, and 0.865 for score 2. Sensitivity for detecting score 0 was particularly high at 0.997. Such conclusions would indicate that this AI model supports and classifies skin irritation effectively, thus allowing for quicker and more accurate skin assessments.

“The AI-based erythema reading model developed in this study demonstrates significant potential to enhance the efficiency of evaluations while minimising inter-rater variability, thereby enabling more objective and consistent assessments,” they wrote.

 “Moreover, the integration of the proposed future improvements is expected to further increase the accuracy and reliability of patch test reaction grading, ultimately broadening the model's applicability across a variety of clinical environments.”

Kim S, Hwang H, Oh M, Han J, Park S, Lee S, Kim G, Cho S, Lee DH, Cho JY. Evaluation of Artificial Intelligence-Assisted Diagnosis of Skin Erythema in a Patch Test. Contact Dermatitis. 2025 Aug 27. 

WH Chan, R Srivastava, N Damaraju, et al. “Automated Detection of Skin Reactions in Epicutaneous Patch Testing Using Machine Learning,” British Journal of Dermatology 185, no. 2 (2021): 456–458.

A novel AI model, YOLO v5, has been developed to classify skin irritation from patch tests, demonstrating high accuracy and efficiency. The model, created by researchers at Sungkyunkwan University, overcomes limitations of traditional CNNs by using an object detection algorithm. The study involved 83,629 images, achieving a classification accuracy of 0.983 and an F1 score of 0.982. The AI model enhances diagnostic consistency and objectivity, with potential improvements expected to increase its applicability in various clinical settings, ultimately improving patch test reaction grading.

This analysis suggests that this AI model effectively classifies skin irritation in patch tests, allowing for quicker and more accurate dermatologic assessments.

Artificial Intelligence Model Effective in Classification of Skin Erythema

A new study found that multi-omics profiling of immune cells revealed molecular drivers of peanut oral immunotherapy responsiveness linked to gastrointestinal mechanisms.

“Taken together, our findings suggest a critical imbalance of robust Treg responses and B cell suppression on the one hand and the dominance of innate immune signaling and metabolic stress on the other as [a] potential mechanism of incomplete desensitization,” wrote study investigator Aleix Arnau-Soler, PhD, a postdoctoral scientist at Max-Delbrück-Center’s pediatric allergy clinic, and colleagues.

The US Food & Drug Administration approved oral immunotherapy for peanuts (Palforzia, formerly AR101) in January 2020.

 Although oral immunotherapy helps desensitize patients to their peanut 

, 15% to 30% of patients do not respond and are at significant risk of anaphylaxis with the treatment.

Investigators conducted a placebo-controlled trial to identify molecular drivers of the responsiveness of oral immunotherapy for peanuts.

The team assessed this via multi-omics profiling in immune cells, analyzing immunoglobulins, cytokines, transcriptome, and DNA methylome profiles before and after treatment in both peanut-stimulated and unstimulated peripheral blood mononuclear cells in children with a peanut allergy.

“Unlike other studies focusing on allergen-specific T cells using CD154-based approaches, they addressed the transcriptome and methylome profiling of whole PBMC bulks, yielding more granular high-level insights into the functional biology of peanut OIT,” wrote Annette Kuehn, PhD, from Luxembourg Institute of Health, and Thomas Eiwegger, MD, from the University of Toronto, in an accompanying editorial.

 “This poses risks and chances in re-visiting more general questions with new state-of-the-art transcriptomic methods by using ‘older’ methods of allergen-specific stimulation, which are less rigid than those performed more recently in this context.”

The study included 49 children (29 boys, 20 girls; mean age, 7 years) with a challenge-proven peanut allergy.

 In total, 27 participants received peanut, and 22 received a placebo; 11 on placebo later switched to peanut. For 14 months, participants in the active arm underwent dose escalation up to the target dose of 125–250 mg of peanut protein, which was then maintained for an additional 2 months.

The study found that complete responders, who tolerated 4500 mg of peanut protein (15 – 30 peanuts), presented lower pre-treatment peanut-specific IgE and Th2 cytokine production (IL-4, IL-5) compared to incomplete responders who tolerated ≤ 1000 mg of peanut protein.

Investigators identified 184 differentially expressed genes and 1001 differentially methylated genes.

 These genes were linked to innate immune cells (ILC3s), adaptive immune cells CD8αα subset of CD8+ T cells), γδ T cells, and exosomes. These findings demonstrate the important role gastrointestinal immune regulation plays in the success of oral immunotherapy.

“Using deep immune phenotyping of PBMC from peanut-allergic patients, gastrointestinal symptoms were associated with gut-migratory immune signatures—marked by Th2, memory regulatory T cells (Tregs) and CD8+ T cell responses—via chemotactic navigation and CD196/CCR6 upregulation, further emphasizing the importance of gut tissue inflammation,” Kuehn and Eiwegger wrote.

The team also observed more changes in DNA methylation than RNA expression linked to a stronger oral immunotherapy response.

“This may be due to methylation changes detected for genes not expressed in [peripheral blood mononuclear cells],” Arnau-Soler and colleagues explained.

The study found that patients receiving peanut oral immunotherapy had a much lower activity of immunoglobulin genes than those receiving a placebo.

 The finding suggests that oral immunotherapy changes how B cells function.

Among patients who responded fully to oral immunotherapy, functional networks showed a stronger regulatory T-cell activity and suppression of B-cell responses.

 However, among incomplete responders, innate immune signaling (NLRP1, HIF-1 signaling pathway) and signs of metabolic stress (hypoxia, glycolysis) dominated the networks.

“The data from Arnau-Soler et al. is highly relevant in pointing toward changes of gut-associated immunity in successful peanut [oral immunotherapy],” Kuehn and Eiwegger concluded.

 “A limitation is that those findings are confirmed at the protein and single-cell level. In the future, it will be required to combine different OMIC approaches exploring both innate and adaptive targets, considering gut immune homeostasis when investigating immunological changes during [oral immunotherapy].”

Arnau-Soler A, Ashley SE, Ghauri A, et al. Understanding the Variability of Peanut-Oral Immunotherapy Responses by Multi-Omics Profiling of Immune Cells. 

. Published online July 22, 2025. doi:10.1111/all.16627

Oral Immunotherapy (OIT) in Practice | Food Allergy Research & Education. Food Allergy Research & Education. 

https://www.foodallergy.org/resources/oral-immunotherapy-oit-practice

Kuehn A, Eiwegger T. Oral Immunotherapy of Peanut Allergy: A Critical Role for Gut-Associated Immunity. 

. Published online August 1, 2025. doi:10.1111/all.16657

Multi-omics profiling of immune cells has identified molecular drivers of peanut oral immunotherapy (OIT) responsiveness, highlighting gastrointestinal mechanisms. The study found that complete responders to OIT exhibited lower pre-treatment peanut-specific IgE and Th2 cytokine production compared to incomplete responders. Differentially expressed and methylated genes were linked to immune cells and exosomes, emphasizing the role of gastrointestinal immune regulation. The study also noted more DNA methylation changes than RNA expression changes, suggesting a significant impact on B cell function and gut-associated immunity in successful OIT.

Research links Treg activity, B-cell suppression, and gastrointestinal immune regulation to the success and failure of peanut oral immunotherapy.


Peanut Oral Immunotherapy Response Linked to Gut Immunity in Children

“Remarkable” Phase 2 Oxylanthanum Carbonate Data, With Pablo Pergola, MD, PhD

Hyperphosphatemia remains a common and clinically important challenge for individuals with 

 undergoing dialysis. Although phosphate binders play a critical role in helping regulate phosphate levels, their utility is often hampered by large pill sizes, high daily pill counts, strict dosing requirements, and gastrointestinal intolerance. These barriers frequently lead to poor adherence, limiting their effectiveness in long-term disease management.

“When you talk about efficacy… there are several things that affect how you can get that done. One is the potency, so how well the medication works in binding the phosphate from the intestine. But a very potent drug that you cannot take doesn't work. If it sits on the counter or on your table, then the efficacy is zero,” Pablo Pergola, MD, PhD, research director of the Clinical Advancement Center at Renal Associates PA, explained to 

. “You need to have something that's potent that the patients can take, so it relates to that pill burden, availability, and accessibility, so the patient can take it, they tolerate it, and it works. Then you get the efficacy that you need.”

Oxylanthanum carbonate (OLC), an investigational lanthanum-based phosphate binder, has been developed using nanoparticle technology designed to minimize pill size and reduce overall pill burden. Findings from a phase 2, open-label, single-arm, multicenter trial published in the 

Clinical Journal of the American Society of Nephrology

 point to OLC’s potential as a promising new therapy for managing hyperphosphatemia in patients with CKD receiving dialysis.1

For more on the shortcomings of current phosphate binders, check out part 1 of the interview with Pergola 

The trial enrolled patients with serum phosphate (sP) ≥4.0 and ≤7.0 mg/dl for ≥ 8 weeks before screening while receiving thrice weekly hemodialysis and a stable phosphate binder regimen. The primary objective was to evaluate the tolerability of OLC at clinically effective doses with a goal sP concentration ≤5.5 mg/dl.

The trial included washout, titration, and maintenance periods. Patients started titration when sP was >5.5 mg/dl and entered maintenance once sP was ≤5.5 mg/dl. The starting dose of OLC during titration was 1500 mg/d (500 mg thrice daily).

A total of 86 patients were treated with OLC during the study. At screening, sP was ≤5.5 mg/dl in 59% of patients. Among the cohort, 91% of patients entered maintenance and 71 achieved sP ≤5.5 mg/dl on a median OLC dose of 500 mg 3 times a day. Of note, two-thirds of patients required ≤ 3 OLC tablets per day to achieve target sP levels, with most requiring no more than one tablet with each meal.

“This is not trivial. I've done multiple studies with phosphate bindings in the past, and I had never seen a drug performed this way. It's really remarkable,” Pergola said. “It's a small study, I understand, but finding this kind of efficacy is unheard of.”

Editors’ note: Pergola has relevant disclosures with Alexion, Ardelyx, AstraZeneca, Bayer, CSL, DISC, Novo Nordisk, Renibus, Unicycive, and Vera.

Unicycive Therapeutics. Unicycive Therapeutics Announces the Publication of Oxylanthanum Carbonate Pivotal Trial Data in Clinical Journal of the American Society of Nephrology. July 24, 2025. Accessed August 28, 2025. 

https://ir.unicycive.com/news/detail/107/unicycive-therapeutics-announces-the-publication-of

Brooks A. Oxylanthanum Carbonate May Offer Desirable Alternative to Current Phosphate Binders. 

. April 10, 2025. Accessed August 28, 2025. 

https://www.hcplive.com/view/oxylanthanum-carbonate-may-offer-desirable-alternative-current-phosphate-binders

Pergola breaks down findings from a phase 2 trial of OLC for managing hyperphosphatemia in patients with chronic kidney disease receiving dialysis.

Paul Heidenreich, MD | Image Credit: Stanford University

On August 26, 2025, the American College of Cardiology released Concise Clinical Guidance (CCG) recommending 

 against a variety of respiratory diseases, including 

The American College of Cardiology's Concise Clinical Guidance recommends vaccines for adults with cardiovascular disease to protect against respiratory diseases like COVID-19, RSV, and influenza. The guidelines emphasize overcoming financial barriers, providing education, and addressing vaccine hesitancy. Specific vaccine recommendations include annual influenza vaccines, COVID-19 vaccines, and one-time pneumococcal and RSV vaccines. The guidelines highlight the importance of clinician-patient discussions and suggest strategies to improve vaccination rates, such as reminders and leveraging insurance systems. Clinicians are encouraged to integrate vaccination into cardiovascular care to enhance patient outcomes.

The 2025 Concise Clinical Guidance also aims to assuage vaccine hesitancy and resistance, provide better education, and overcome barriers to implementation.

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