"Cedar Fever" hits Central Texas again: allergic rhinitis/conjunctivitis in December-February

From the local ABC TV station:

Just the sight of cedar is enough to make Millie Stefonsky start itching: "Itchy eyes, very watery eyes, scratchy throat, not having that energy we all need."

After years of fighting cedar fever, Stefonsky tried allergy shots and says they've made a world of difference. "I swear by it. I think that's the best way to go," she says.



Here are the Treatment Options for Allergic Rhinitis and Non-Allergic Rhinitis (click to enlarge the image):



Ocular antihistamines (eye drops) (click to enlarge the image):



References:

"Cedar Fever" hits Central Texas


Treating rhinitis improves asthma symptoms

Allergic rhinitis, especially when persistent (PER) and associated with asthma heavily impairs patients' quality of life (QoL). This Italian study assessed the effect of mometasone furoate nasal spray (MFNS) on the QoL of patients with PER and asthma.

52 adults patients used momethasone 200 μg/day or placebo for 28 days.

The total 5-symptom score (T5SS) for rhinitis, the asthma symptom score and the sum of the two [global symptoms score (GSS)] were recorded daily. The primary outcome was the change in the Rhinasthma global summary (GS) at the end of treatment.

Momethasone produced a significant change in the Rhinasthma GS and improved symptoms.

The authors concluded that in in patients with PER rhinitis and intermittent asthma, momethasone nose spray improves the QoL and the burden of respiratory symptoms. Treating rhinitis may affect the asthma-related QoL.

Limitations of the study: The study relied only on subjective criteria such as patient symptoms, and no objective criteria such as FEV1 were included in the assessment of respiratory function.



Severe asthma (click to enlarge the image).

References:

Effects of mometasone furoate on the quality of life: a randomized placebo-controlled trial in persistent allergic rhinitis and intermittent asthma using the Rhinasthma questionnaire. Clin Exp Allergy. 2010 Dec 1. doi: 10.1111/j.1365-2222.2010.03660.x. Baiardini I, Villa E, Rogkakou A, Pellegrini S, Bacic M, Compalati E, Braido F, Le Grazie C, Canonica GW, Passalacqua G.

Image source: Illustration for "Aquiline or Roman Nose", Wikipedia, GNU Free Documentation License.


Children with allergic and nonallergic rhinitis have a similar risk of asthma: 20%

This study included 38 seven-year-old children with allergic rhinitis, 67 with nonallergic rhinitis, and 185 without rhinitis from the Copenhagen Prospective Study on Asthma in Childhood birth cohort. They were compared for prevalence of asthma, eczema, food sensitization, filaggrin null-mutations, total IgE, blood eosinophil count, fractional exhaled nitric oxide (FeNO), lung function, and bronchial responsiveness.

Children with allergic rhinitis compared with asymptomatic controls had increased prevalence of:

- asthma (21% vs 5%),
- food sensitization (47% vs 13%)
- eczema (66% vs 43%)
- increased total IgE (155 kU/L vs 41 kU/L)
- blood eosinophil count (0.46 x 10(9)/L vs 0.30 x 10(9)/L)
- FeNO (15.9 ppb vs 6.6 ppb)
- bronchial hyperresponsiveness (23% vs 9%)

Children with nonallergic rhinitis also had increased asthma prevalence (20% vs 5%) but showed no association with eczema, food sensitization, total IgE, blood eosinophil count, FeNO, or bronchial responsiveness.

The study authors concluded that asthma is similarly associated with allergic and nonallergic rhinitis, suggesting a link between upper and lower airways beyond allergy-associated inflammation.



Modified Asthma Predictive Index (API) (click to enlarge the image).

References:

Children with allergic and nonallergic rhinitis have a similar risk of asthma. Chawes BL, Bønnelykke K, Kreiner-Møller E, Bisgaard H. J Allergy Clin Immunol. 2010 Sep;126(3):567-573.e8.


SPT < 7mm and sIgE < 2kU/L identify children likely to tolerate peanut (only 5% likelihood of failing oral challenge)

A growing number of preschool children are identified as peanut sensitized in the course of investigation of other allergic conditions. But are they "truly allergic"? Although many have never ingested peanuts and their clinical reactivity is not known, it has been common practice to place these children on avoidance diets for many years.

This Australian study aimed to determine the utility of skin prick tests (SPT) and fluorescent-enzyme immunoassays (FEIA) for identifying either peanut allergy or tolerance in preschoolchildren with peanut sensitization.

49 preschool children (younger than 5 years of age) with peanut sensitization (defined as SPT larger than 2 mm or peanut-specific IgE greater than 0.35 kU/L) but unknown clinical reactivity had graded open peanut challenges reaching a total of 11 grams. A positive challenge was defined as an IgE-mediated reaction during challenge or the 2-h observation.

49% of children had positive challenges. An SPT greater than 7 mm on the day of challenge predicted a positive challenge with a sensitivity of 83% and a negative predictive value (NPV) of 84%.

sIgE greater than 2.0 kU/L showed a sensitivity of 79% and an NPV of 80%.

The tests worked much better when combined. Predicting challenge outcome from a combination of SPT and FEIA (SPT greater than 7 mm and/or FEIA  greater than 2) increased sensitivity to 96% and NPV to 95%.

At least half of preschool children with peanut sensitization and no history of peanut ingestion can tolerate peanuts.

A SPT less than 7 mm and FEIA less than 2 kU/L identify children most likely to tolerate peanut, with only a 5% likelihood of failing an oral challenge. This study would definitely help allergists when considering oral challenges in peanut-sensitized children.


8 top allergens account for 90 percent of food allergies. Specific IgE levels (sIgE) that predict the likelihood of passing an oral food challenge are shown in the figure. (click to enlarge the image).

References:

Skin prick testing and peanut-specific IgE can predict peanut challenge outcomes in preschoolchildren with peanut sensitization. Johannsen H, Nolan R, Pascoe EM, Cuthbert P, Noble V, Corderoy T, Franzmann A, Loh R, Prescott SL. Clin Exp Allergy. 2011 Mar 24. doi: 10.1111/j.1365-2222.2011.03717.x.
Food Allergen Avoidance
Food Challenges
Mind Maps: Food Allergy
Image source: Roasted peanuts as snack food, Wikipedia, public domain.


Asthmatics who slept beneath the stream of cool air device for one year had improved quality of life and decreased airway inflammation

A randomized, double-blind, placebo-controlled trial evaluated whether environmental control with nocturnal temperature controlled laminar airflow (TLA) treatment could improve the quality of life of 300 patients aged 7–70 with inadequately controlled persistent atopic asthma in 19 European asthma clinics. TLA devices were installed in the bedrooms of patients to provide a stream of cool air above their heads (see the video embedded below).



The manufacturer advertises the device, called Protexo, as "treatment for patients with atopic asthma without side-effects" (video).

There was a statistically significant difference in treatment response rate between active (76%) and placebo (61%) groups (p=0.02). There was also a difference between groups in fractional exhaled nitric oxide (FeNO) change of −7.1 ppb (p=0.03). Interestingly, the nocturnal temperature controlled laminar airflow (TLA) was associated with less increase in cat-specific IgE than placebo.

The study authors concluded that TLA improves quality of life, airway inflammation and systemic allergy in patients with persistent atopic asthma. Even if the benefits of TLA are confirmed in future trials, the expected relatively high cost of the device (Protexo) may be problematic. A similar device (Opragon) by the same Swedish company (Airsonett) is used to reduce surgical site infections. Neither device is available in the U.S.

References:

Nocturnal temperature controlled laminar airflow for treating atopic asthma: a randomised controlled trial. Thorax doi:10.1136/thoraxjnl-2011-200665

Comments from Twitter:

Jennifer Gunter @DrJenGunter: re: cool air device, is that like heading for "sea air" as docs of yore recommended?

@Allergy: Protexo is a bit different - it probably changes the exposure to indoor rather than outdoor allergens


RNA interference (RNAi) - by Nature Video

RNA interference (RNAi)is used by many different organisms to regulate the activity of genes. This animation explains how RNAi works and introduces the two main players:

- small interfering RNAs (siRNAs)
- microRNAs (miRNAs)

The Nature video takes you on an audio-visual journey, diving into a cell to show how genes are transcribed to make messenger RNA (mRNA) and how RNAi can silence specific mRNAs to stop them from making proteins.


Chronic Rhinosinusitis (CRS)

Chronic rhinosinusitis (CRS) affects 12.5% of the US population.

Risk factors for CRS

The following associations are found between CRS prevalence and:

- air pollution
- active cigarette smoking
- secondhand smoke exposure
- perennial allergic rhinitis
- gastroesophageal reflux (GERD)

The majority of pediatric and adult patients with CRS are immune competent (editor note: this has been challenged recently by a study that showed that more than 70% of adult patients with chronic sinusitis may have a poor response to pneumococcal immunization).


Nose and nasal cavities. Image source: Wikipedia, public domain.

Classification of CRS

- CRS without nasal polyposis (CRSsNP)
- CRS with nasal polyposis (CRSwNP)
- allergic fungal rhinosinusitis (AFRS)

Treatment of CRS

The highest level of evidence for treatment for CRSsNP exists for saline lavage, intranasal steroids, and long-term macrolide antibiotics.

The highest level of evidence for treatment of CRSwNP exists for intranasal steroids, systemic glucocorticoids, and topical steroid irrigations.

Aspirin desensitization is beneficial for patients with aspirin-intolerant CRSwNP.

Sinus surgery followed by use of systemic steroids is recommended for AFRS.

Other modalities of treatment, such as antibiotics for patients with purulent infection and antifungal drugs for patients with AFRS, are potentially useful despite a lack of evidence from controlled trials.

References:

Chronic rhinosinusitis: Epidemiology and medical management. Hamilos DL. J Allergy Clin Immunol. 2011 Sep 2.


Daily vs. Intermittent Budesonide in Preschool Children with Recurrent Wheezing: No Difference

Daily inhaled corticosteroids are recommended for young children at risk for asthma exacerbations and an exacerbation in the preceding year. However, concerns remain about effects on growth. This study published in the NEJM compared daily therapy with intermittent therapy with nebulized budesonide in 278 children aged 12 to 53 months. All of them had positive modified asthma predictive index (API), recurrent wheezing episodes, and at least one exacerbation in the previous year but a low degree of impairment.



Modified Asthma Predictive Index (API) (click to enlarge the image).

They were randomly assigned to receive a budesonide inhalation suspension for 1 year as either an intermittent high-dose regimen (1 mg twice daily for 7 days, starting early during respiratory tract illness) or a daily regimen (0.5 mg nightly).

The daily regimen of budesonide 0.5 mg did not differ significantly from the intermittent regimen with in terms of exacerbations or adverse events.

The authors concluded that a daily low-dose regimen of budesonide 0.5 mg was not superior to an intermittent high-dose regimen (1 mg twice a day) in reducing asthma exacerbations. This is an important development especially considering that the mean exposure to budesonide was 104 mg less with the intermittent regimen.



Asthma Inhalers (click to enlarge the image).

References:

Daily or Intermittent Budesonide in Preschool Children with Recurrent Wheezing. N Engl J Med 2011; 365:1990-2001, November 24, 2011.


No dose-response relationship for fluticasone furoate in moderate/severe asthma: 200 mcg once daily worked as well as 800 mcg

Fluticasone furoate (FF) is a new inhaled corticosteroid with 24-hour activity. GlaxoSmithKline is developing FF as a once-daily asthma treatment in combination with the long-acting β2 agonist vilanterol.

This 8-week multicentre, randomized, double-blind study included 600 adult patients with persistent moderate-to-severe asthma, who were symptomatic on medium-dose inhaled corticosteroid therapy. The study was sponsored by GlaxoSmithKline and company employees were among the co-authors.

The patients were randomized to placebo, FF 200, 400, 600 or 800 μg (once daily in the evening using a new dry powder inhaler), or fluticasone propionate 500 μg twice daily (via Diskus or Accuhaler).


Fluticasone furoate, Veramyst (US) and Avamys (EU and Canada), is different in structure from fluticasone propionate (see below). Image source: Wikipedia, public domain.


Fluticasone propionate, Flonase (US and Canada) Flixonase (EU and Brazil). Fluticasone propionate is also part of the ICS/LABA combination product Advair. Image source: Wikipedia, public domain.

Each inhaled steroid dose was superior to placebo for the primary endpoint which was pre-dose evening forced expiratory volume in one second (FEV1). There was no dose–response relationship across the FF doses studied. Peak expiratory flow improved in all groups. The incidence of oral candidiasis was higher with FF 800 μg than placebo; there was also a higher systemic exposure of FF at this highest dose level.

The study authors concluded that FF doses below 800 μg have a favorable therapeutic index, and 200 μg is an appropriate dose in patients with moderate persistent asthma.

References:

Fluticasone furoate demonstrates efficacy in patients with asthma symptomatic on medium doses of inhaled corticosteroid therapy: an 8-week, randomised, placebo-controlled trial. Thorax 2012;67:35-41 doi:10.1136/thoraxjnl-2011-200308


Inhaled steroids associated with 34% increase in the rate of diabetes?

Systemic corticosteroids are known to increase diabetes risk, but the effects of high-dose inhaled corticosteroids are unknown.

This study from Canada included a cohort of almost 400,000 patients treated for respiratory disease during 1990-2005. They were identified using the Quebec health insurance databases and followed through 2007 or until diabetes onset.

Current use of inhaled corticosteroids was associated with a 34% increase in the rate of diabetes (rate ratio [RR] 1.34) and in the rate of diabetes progression (RR 1.34).

The risk increases were greatest with the highest inhaled corticosteroid doses, equivalent to fluticasone 1,000 mcg per day or more (RR 1.64)

The study authors concluded that inhaled corticosteroid use is associated with modest increases in the risks of diabetes onset and diabetes progression. The risks are more pronounced at the higher doses, currently prescribed in the treatment of chronic obstructive pulmonary disease (COPD).

The risk is small and patients must not stop taking their asthma medications without discussing it with their doctor.


Anti-diabetes medications Avandia and Actos are peroxisome proliferator-activated receptor-γ (PPARγ) agonists that have anti-inflammatory effects and are currently in clinical trials for treatment of asthma.

References:

Inhaled Corticosteroids and the Risks of Diabetes Onset and Progression. The American Journal of Medicine, Volume 123, Issue 11, Pages 1001-1006, November 2010.

Comments from Twitter:

@sdietrich17 (Sharon Dietrich): Is there no end of "good" news about drugs we trusted and worked well for their purpose?? Discouraging!!

@DrVes: look at it from another angle - we know a lot more about the drugs that have been in use for 30+ years now... including both safety profile and side effects. Knowing the side effects that occur even in a small group of patients would make the physicians more vigiliant. Also, it would help to target the medication to a particular group of patients that is likely to benefit most from it.

@sdietrich17 (Sharon Dietrich): Understood, of course. But we were told for years that absorption of inhaled steroids was not enough to cause diabetes --and they work!!


Inhaled steroids for 6 months may affect bone status of female asthmatic patients

The effect of inhaled corticosteroid (ICS) on the bone status of asthmatic patients is still uncartain. In this Japanes study, the bone status of ICS users with asthma with ultrasound measurements of calcaneus with AOS-100.

The ratio of the osteo sono-assessment index (OSI) to the average OSI corrected for age and gender was noted. The second %OSI measurement was performed 6 months after the first %OSI one.

During the 6-month study period, individual treatment remained unchanged.

There were no differences in the 1st and 2nd %OSI between the ICS users and control subjects. However, the 2nd %OSI decreased compared with 1st %OSI in female ICS users. There were no changes in the male ICS users.

The researchers concluded that 6 month management of asthma with regular ICS use, might have a harmful influence on the bone status of female asthmatic patients.



Asthma Inhalers (click to enlarge the image).

References:

Assessment of Bone Status in Inhaled Corticosteroid User Asthmatic Patients with an Ultrasound Measurement Method. Sasagawa M, Hasegawa T, Kazama JI, Koya T, Sakagami T, Suzuki K, Hara K, Satoh H, Fujimori K, Yoshimine F, Satoh K, Narita I, Arakawa M, Gejyo F, Suzuki E. Allergol Int. 2011 June.
Image source: Flickr, Creative Commons license.

Comments from Twitter:

CERTIFIED Allergy @allergysa: I'm going to have to calculate what the actual ATTRIBUTABLE risk would be. I've never liked relative risk as a measuring stick.


SCIT ("allergy shots") linked to lower of incidence of autoimmune disease, ischemic heart disease, and mortality

Subcutaneous allergen-specific immunotherapy (SCIT) is a well-documented treatment of IgE-mediated allergic disease with 100-year history. However, little is known about potential effects of SCIT on the risk of other chronic immune-related diseases.

Researchers from Denmark investigated the association of SCIT with the incidence of autoimmune disease and ischemic heart disease (IHD), and all-cause mortality.

All Danish citizens were followed through central registries on medications and hospital admissions during the 10-year study period. The study compared mortality and development of autoimmune diseases, acute myocardial infarction (AMI), and IHD in:

- persons receiving SCIT
- persons receiving conventional allergy treatment (CAT; nasal steroids or oral antihistamines)

Receiving SCIT was associated with:

- lower mortality (HR, 0.71)
- lower incidence of AMI (HR, 0.70)
- lower incidence of IHD (HR, 0.88)
- lower incidence of autoimmune disease (HR, 0.86)

Receiving SCIT compared with conventional allergy treatment (nasal steroids or oral antihistamines) was associated with lower risk of autoimmune disease and AMI, as well as decreased all-cause mortality.


Mechanisms of allergen-specific immunotherapy (click to enlarge the image). CD27 expression on allergen-specific T cells may be a new surrogate for successful allergen-specific immunotherapy (JACI, 2012).

References:

Association of subcutaneous allergen-specific immunotherapy with incidence of autoimmune disease, ischemic heart disease, and mortality. Linneberg A, Jacobsen RK, Jespersen L, Abildstrøm SZ. J Allergy Clin Immunol. 2011 Oct 15.

Image source: OpenClipArt.org, public domain.


Oral food challenge with baked milk

According to Dr. Nowak-Wegrzyn from Jaffe Food Allergy Institute at Mount Sinai School of Medicine, the suggested exclusion criteria for oral food challenge with baked milk are:

- serum cow milk-IgE greater than 35 kUA/L because most (although not all) of the children with levels higher than 35 kUA/L reacted to baked milk and they tended to have more severe reactions during the baked milk challenge.

- children who had life-threatening anaphylaxis to milk within past 2 years.

- history of a convincing allergic reaction to small amount of baked milk in the past 6 months. "Allergic reaction" includes immediate symptoms within minutes to 1 hour of ingesting the food such as hives, angioedema, rhinorrhea, wheezing, cough, SOB, emesis, diarrhea).

One has to be even more careful with the outpatient challenge and choose a more conservative cut-off level, e.g. cow's milk IgE less than 5 kUA/L or cow's milk (CM) skin prick test wheal less than 9 mm.


Oral Food Challenges (click to enlarge the diagram).

How to perform the challenge with baked milk?
Here is a sample protocol for challenge with baked milk from Mount Sinai Research Center, published in JACI, 2008: Heated milk challenges were performed openly. Each muffin and waffle contained 1.3 g milk protein (nonfat dry milk powder; Nestle Carnation, Glendale, Calif).

The muffin was baked at 350°F for 30 minutes in an oven, and the waffle (less than 0.625 inches thick to ensure thorough heating) was cooked in a waffle maker at approximately 500°F for 3 minutes.

Each food was administered in 4 equal portions over 1 hour. The muffin was served first; if no symptoms were observed, 2 hours later, the waffle was served.

Patients were monitored throughout and for 2 to 4 hours after the completion of the final challenge. Challenges were discontinued at the first objective sign of reaction, and treatment was initiated immediately (source: The Journal of Allergy and Clinical Immunology, Volume 122, Issue 2, Pages 342-347.e2, August 2008).

References:


Baked Milk Challenges. AAAAI Ask the Expert, 2011.
Challenge to baked milk - casein IgE <0.7 kUA/L is a favorable prognostic factor for tolerance of baked milk  http://goo.gl/OAiiY
Food Challenges for Diagnosis of Food Allergy
Rare, medium, or well done? Effect of heating on food protein allergenicity http://goo.gl/Z4LbX - It definitely affects milk and egg products.
Image source: Cookie, openclipart.org, public domain.


Immunostimulant Broncho-Vaxom (OM-85 BV) prevents wheezing attacks in preschool children

The effect of the immunostimulant OM-85 BV was assessed in preventing acute respiratory tract illnesses (ARTIs)-provoked wheezing attacks in preschool children with recurrent wheezing. OM-85 BV (Broncho-Vaxom) was provided by OM Pharma, Geneva, Switzerland. It is not a new drug and it has been available in Europe for more than 30 years. OM-85 BV consists of extracts of 8 types of bacteria thought to be important in respiratory infections. It is administered orally.

One capsule for children contains: 3,5 mg of lyophilized bacterial lysates of Haemophilus influenzae, Diplococcus pneumoniae, Klebsiella pneumoniae and ozaenae, Staphylococcus aureus, Streptococcus pyogenes and viridans, Neisseria catarrhalis.

A randomized, double-blind study included 75 children with recurrent wheezing who were 1 to 6 years old. They were given either OM-85 BV or a placebo (1 capsule per day for 10 days each month for 3 months).

Subjects given OM-85 BV had a 38% reduction in the rate of wheezing attacks.


The main difference between the OM-85 BV and placebo groups was a reduction the number of ARTIs. The duration of each wheezing attack was 2 days shorter in the group given OM-85 BV.

Administration of OM-85 BV (Broncho-Vaxom) reduced the rate and duration of wheezing attacks in preschool children with ARTIs.

Broncho-Vaxom is not yet available in the U.S.A. or Canada.

References:

The immunostimulant OM-85 BV prevents wheezing attacks in preschool children. J Allergy Clin Immunol. 2010 Oct;126(4):763-9.

Broncho-Vaxom

Comments from Facebook:

Kay Walker: Sounds ideal for kids & others! As a kid, I caught EVERY germ within 100kms, they ALWAYS developed into wheezes that developed into bronchitis/pneumonia/pleurisy & eventually, adrenaline injections (that's all there was). If it worked it would have changed my life totally. Must investigate!


Maternal contact with farm animals and cats during pregnancy may protect against atopic dermatitis in children

Studies have suggested that prenatal farm exposures might protect against allergic disease and increase the expression of receptors of the innate immune system.

1,000 children articipated in a birth cohort study in Switzerland. Doctor-diagnosed atopic dermatitis was reported by the parents from 1 to 2 years of age, Gene expression of Toll-like receptors (TLRs) and CD14 was assessed in cord blood leukocytes by quantitative PCR.

Maternal contact with farm animals and cats during pregnancy had a protective effect on atopic dermatitis in the first 2 years of life. The risk of atopic dermatitis was reduced by more than half among children with mothers having contact with 3 or more farm animal species.


Elevated expression of TLR5 and TLR9 in cord blood was associated with decreased prevalence of atopic dermatitis.

Maternal contact with farm animals and cats during pregnancy has a protective effect on the development of atopic dermatitis in early life.


Pathogen Recognition Receptors, TLRs. This video is from: Janeway's Immunobiology, 7th Edition Murphy, Travers, & Walport. Source: Garland Science.

References:

Prenatal animal contact and gene expression of innate immunity receptors at birth are associated with atopic dermatitis. Roduit C, Wohlgensinger J, Frei R, Bitter S, Bieli C, Loeliger S, Büchele G, Riedler J, Dalphin JC, Remes S, Roponen M, Pekkanen J, Kabesch M, Schaub B, von Mutius E, Braun-Fahrländer C, Lauener R; PASTURE Study Group. J Allergy Clin Immunol. 2010 Nov 26.

Toll-like receptors (TLRs) and CD14

Protective role of contact with livestock and farming lifestyle on asthma, in particular during childhood. ERJ January 1, 2012 vol. 39 no. 1 67-75.

Image source: OpenClipArt.org, public domain.


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