Should all patients with severe asthma get tested for AAT deficiency?


α1-Antitrypsin (A1AT). Image source: Wikipedia, GNU Free Documentation License.

There is an uncertain relationship between severe AAT deficiency and asthma. Studies have not shown an increased prevalence of AAT deficiency among asthmatics. There is no association of alpha-1 antitrypsin Pi variants such as Pi MZ or Pi MS with more severe asthma.

However, in a large cohort study of over 1000 patients with severe AAT deficiency, 21% of patients had asthma. The presence of asthma was not independently associated with an accelerated decline in pulmonary function, and the results of augmentation therapy appear to be similar for asthmatics and nonasthmatic patients with severe AAT deficiency.

Should patients with severe asthma get tested for AAT deficiency?

For some patients, yes. For the lifelong non-smoker with persistent and irreversible airflow obstruction, a one-time measurement of the serum alpha-1 antitrypsin level is recommended to exclude emphysema due to homozygous alpha-1 antitrypsin deficiency, which is in the differential of chronic and largely irreversible airflow limitation.

References:

Evaluation of severe asthma in adolescents and adults. UpToDate, 2014.
Diagnosis of asthma in adolescents and adults. UpToDate, 2014.
Eden E, Hammel J, Rouhani FN, et al. Asthma features in severe alpha1-antitrypsin deficiency: experience of the National Heart, Lung, and Blood Institute Registry. Chest 2003; 123:765.
http://www.ncbi.nlm.nih.gov/pubmed?term=12628876

What is the word origin of allergy and asthma conditions?

Google dictionary card has etymological information, a translation box and a graph that shows the use of a word over time. If you only want to find the origin of a word like "allergy", you don't have to search for [define allergy]. You can search for [allergy origin] or [allergy word origin] and Google shows a special version of the dictionary card that highlights etymological information. Google Search Card results for "Word Origin" for common allergy and asthma conditions are shown below. You can see them all in the slideshow, or click through the links:

allergy
asthma
urticaria
anaphylaxis
dermatitis
atopic



allergy



asthma



References:

Word Origin Google Search Card http://bit.ly/1CqBXfr
Google Updates the Dictionary OneBox http://bit.ly/1CqBYjI

Top Asthma Articles for January 2015

Here are my suggestions for some of the top articles about asthma published recently:

Asthma and Allergen Sensitization start earlier in life than previolsy reported (age 2 for asthma, age 1 for allergy), dust mite is the culprit in 80% http://buff.ly/1uU6P5u

Exercise-induced bronchoconstriction (EIB) underdiagnosis may result in habitual avoidance of sports and physical activity, chronic deconditioning, weight gain, poor asthma control, low self-esteem, and reduced quality of life. Improving EIB diagnosis: no existing EIB screening questionnaire had adequate sensitivity and specificity http://buff.ly/1k1KEFT

Vitamin D supplementation in adults with asthma is not indicated - VIDA RCT http://buff.ly/1hZ1KzT

Humanized monoclonal antibody (AMG 157) against a novel target in human asthma, thymic stromal lymphopoietin (TSLP) http://buff.ly/1knrvON

Irritant-induced (occupational) asthma (IIA) - EAACI position paper http://buff.ly/1omacyu

Climate change and respiratory diseases http://buff.ly/1k8txiB (free full text)

Childhood asthma phenotypes in the twenty-first century http://buff.ly/1k8tHX5 (free full text)

The role of macrolides in asthma - The Lancet Respiratory Medicine http://buff.ly/1lRmbUC (free full text after registration)

Quilizumab: New Inhaled Drug Shows Promise Against Asthma, Allergies http://buff.ly/1mXuLSF

Thiazolidinediones may provide a new anti-inflammatory approach to asthma http://buff.ly/1r14W4x

Revisiting an Old Therapy: Theophylline in Asthma http://buff.ly/1r1aXhI

Omalizumab may have anti-inflammatory effects on small airways and reverse airway remodeling http://buff.ly/1r1bccG

Impact of azithromycin therapy on airway microbiota in asthma: decreased bacterial richness, Anaerococcus dominant http://buff.ly/1vOM5df

Survey of 8,000 asthma patients: poor control in 45%, yet most regarded their asthma as not serious and controlled http://buff.ly/1qLVDaX

EHR–Generated Interventions to Reduce Asthma Risk: Seeing the Glass Half Full http://buff.ly/1yrkphB

Children treated daily with ICS grow 0.5 cm less during the first year of treatment, no difference second year http://buff.ly/1jSwb1f

Nebulizers are everywhere, despite years of research showing that MDIs are equivalent with lower cost/side effects http://buff.ly/Uoefj6

In elderly asthmatics, vitamin D supplementation for 12 weeks improved ACT scores http://www.aacijournal.com/content/10/1/48



Severe asthma: “What to do when asthma is not doing well?” (click to enlarge the image).

The articles were selected from Twitter @Allergy and RSS subscriptions. Some of the top allergy accounts on Twitter contributed links. I appreciate the curation provided by @Aller_MD @IgECPD @DrAnneEllis @mrathkopf @MatthewBowdish.

Please feel free to send suggestions for articles to AllergyGoAway AT gmail DOT com and you will receive an acknowledgement in the next edition of this publication.

Using the Ellipta Inhaler Device - training video from National Jewish Health

Get step-by-step instructions for how to use the Ellipta inhaler, a device containing medication to treat COPD and asthma.


Cough in Children and Adults - Twitter summary from 2014 #ACAAI meeting

Dr Bowdish: "Just as a disclaimer, we have a "Cough Center" in our clinic so this is of special interest to me."

Dr Goldsobel says chronic cough patients have been some of the most challenging cases he's had in his practice. However, they are also the most appreciative when you help them, and most of the time that is definitely possible.

Cough is a normal and necessary reflex to expel foreign particles. But it can also be a sign of disease. Sometimes cough, especially in children, is present when it should not be but is still NOT a sign of disease.

Chronic cough can have a tremendous negative impact on lifestyle. Patients with chronic cough score higher on screens for anxiety and depression. Dr Bowdish: Let me second that. I've heard patients who will not go to a movie/theater, out to a restaurant or to church because of their cough.

Excluding normal check-ups, acute cough is the #1 reason for outpatient visits in the US. Chronic cough affects somewhere between 11-20% of the population at some point in their life.

Definition

ACCP classification on cough: In adults, 0-3 weeks = acute cough, 3-8 weeks = subacute, greater than 8 weeks = chronic. There is some controversy about timing in kids, with Dr Ann Chang (from Australia) arguing chronic peds cough if more than 4 weeks. The ACCP has published two reviews of chronic cough. The last one was published in 2006 http://t.co/9FBySAjUf1. Dr Goldsobel notes the ACCP is currently publishing their third series of review articles now, although in piecemeal fashion.



Differential diagnosis of cough. Click here to enlarge the image

Causes

Acute cough is almost always infectious (mainly viral).

Subacute cough is almost always post-infectious cough syndrome. Post-infectious cough (aka post-viral cough) is thought due to heightened cough reflex sensitivity.

Pertussis (aka the "100 Day Cough") is a common cause of post-infectious cough. Declining vaccination rates are the main cause for why we are seeing Pertussis now, but acellular vaccine may not work as well as older patients. By the time they get to us, nasal swabs/serology for Pertussis are not likely helpful.

Dr Goldsobel: Richard Irwin a big cough doc and he has estimates for causes of chronic cough - 40% UACS, 25% Asthma, 20% GERD. Dr Irwin says there is overlap in causes in ~25% of chronic cough patients, ie more than one of the three main causes (UACS, Asthma, GERD). Dr Bowdish: I would not be surprised if there is even more overlap than that. In kids, there’s a 4th type, very wet cough with thick neutrophilic secretions +/- TBM, adenovirus is thought to initiate this.

UACS = Upper Airway Cough Syndrome, new term for post-nasal drip. It accounts for nasal allergies, sinusitis, even tonsillar hypertrophy.

Dr Goldsobel: Patients are mostly off ACE inhibitors by the time they see him, so he PCPs are very good at identifying that trigger now. Dr Goldsobel says it can take 6 weeks for cough to resolve after stopping ACE inhibitors.

Dr Goldsobel notes "asthma" cause includes classical asthma, cough variant asthma, and eosinophilic bronchitis.

Eosinophilic bronchitis includes all features of asthma (eNO, response to steroids, etc) but patients don’t have significant reversibility. So, they don’t do particularly well with bronchodilators but great with ICS/prednisone.

GERD

Dr Goldsobel feels GERD is the most difficult of the three most common causes to diagnose and treat. Diagnosis of GERD is often made retrospectively after trial of antacid regimen (PPI, H2 blockers or both). But patients can have 'acidic' GERD, 'weakly acidic' GERD and 'non-acidic' GERD. You may need impedance probes to know for sure. Extra-esophageal symptoms of GERD (ie cough) can take longer to resolve with PPIs/H2s than esophageal symptoms (up to 1-3 mos). Dr Goldsobel uses twice daily PPI AND H2 blockers for maximal management of GERD-triggered chronic cough. Now, some studies are making things even more complicated, showing cough-variant asthma can cause GERD - chicken or egg? Some non-acidic GERD patients end up with fundoplication for their chronic cough.

It is important to have good specialists (ENT/GI/Pulmonary) available who can help with Dx/Tx and are interested in chronic cough.

Other causes: heart disease, foreign bodies (esp kids), lung diseases, lung cancers (a rare cause in A/I practice because usually CXR is done before the patients comes to you).

Don't forget about sleep apnea can cause of chronic cough. Apneic periods damage laryngeal/pharyngeal tissues.

Idiopathic cough

Idiopathic chronic cough is common among the 10-15% "Other" category - it may be as high as 40% of those. Idiopathic cough is mainly a "neurogenic" cough, where cough receptors are unusually sensitive, usually due to viral damage. Neurogenic cough has many names: habit, tic, irritable larynx, post-viral laryngeal neuropathy, laryngeal sensory neuropathy. Neurogenic cough is treated with nortriptyline, amitriptyline, pregabalin, gabapentin, even nebulized lidocaine. Nebulized lidocaine (4% lidocaine without preservatives b.i.d.) comes from studies where Mayo's Loren Hunt used it for asthma. Here's Dr Hunt's paper on nebulized lidocaine for asthma http://t.co/2lRUKtoIyh.

Dr Goldsobel has used nebulized lidocaine in some patients on a temporary basis to break cough reflex firing in an infinite loop. A big concern with nebulized lidocaine is laryngeal anesthesia so he recommends no eating/drinking 1 hour after using it.

Dr Kaiser Lim also evidently describes nebulized lidocaine in his recent JACI review on Neurogenic Cough http://t.co/yLv6w2hTwH

Dr Goldsobel will use methacholine challenges in patients with normal eNO and still coughing after initial treatment.

Diagnosis

Standard work-up: CXR (if not done in 2-3 yrs), spirometry, FeNO, allergy testing, reviewing for cough-inducing meds (ACEI).

Treatment is directed at possible triggers, but given overlap, he often treats multiple triggers at once.

Related:

P2X3 receptor antagonist (AF-219) in refractory chronic cough: a randomised, double-blind, placebo-controlled phase 2 study : The Lancet http://buff.ly/1pvFuY3

Dr Bowdish: Well, after 3.5 days and 26 units of CME, that's it for me at #ACAAI 2014. It's been great interacting with everyone near & far. It's also been a joy to interact with some of the 'most expert experts.' Discussing these topics in the leaders of their respective diseases has been education and inspiring. Is there anyone better to bounce ideas about my mastocytosis pts than Mariana Castells? Or to learn eczema pointers from Drs. Lio or Boguniewicz? Or how about presenting tough cough patients to an Alan Goldsobel? These are amazing docs who are doing amazing things. And I appreciate being able to present their ideas to you and engaging in online discussions. And thanks again to the @ACAAI for putting on a great conference, and for promoting me to fellowship. Adios Atlanta!

The Twitter summary was made possible by @MatthewBowdish

Several allergists did a great job posting updates from the 2014 meeting of the #ACAAI. I used the website “All My Tweets” to review the tweets. For comparison, here are the tweets from previous #ACAAI meetings (scroll down the page for the past years): http://allergynotes.blogspot.com/search/label/ACAAI

And... this is the end of the series of Twitter summaries from 2014 ACAAI meeting. There will be a similar edition from the upcoming 2015 AAAAI meeting, so stay tuned and subscribe to this blog and Twitter account @Allergy.
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