Management of the Allergic Patient: The Role of a Changing Environment.
In late 2012, one of the authors (DS) started to observe unexpected results when testing patients for inhalant allergens with the Intradermal Dilutional Test (IDT) even though no changes in testing protocols or personnel had occurred. At the same time the management of these patients became more challenging.
New Jersey, where the practice is located, was affected by two severe hurricanes. The first one in 2011 (Irene) and the second one in 2012 (Sandy). Perhaps these storms changed the environment in such a way that patients became more reactive.
The changes in skin reactivity during Intradermal Dilutional Test (IDT) from before and after the hurricanes above described were studied, and the results published in two reports: the first one for dust, dander and pollen, published in 2015,' and the second one for molds, published in 2017. (2) The findings included the following:
* Larger than usual wheals during testing. A positive (reactive) wheal usually measures 7-11 mm. In late 2012, abnormal wheals with diameters of 15-20 mm and more were observed with increased frequency during usual testing sessions for dust, dander, and pollen allergens but not so frequently for mold allergens.
* Skin reactivity to very diluted allergen concentration. According to the allergenic concentration required to elicit a skin response, a patient (or allergen being tested) can be classified as a high reactor or as a low reactor. A high reactor requires a weak-diluted concentration of allergen to elicit a positive response in the allergy test (dilutions #4, #5 or #6). A low reactor requires a strong concentration of allergen to elicit a skin response (dilutions #3, #2 or #1). For allergen extracts that are available as 1:20 wt/vol, the six dilutions contain an allergenic concentration of: 1:100 for dilution #1; 1:500 for dilution #2; 1:2500 for dilution #3; 1:12,500 for dilution #4; 1:62,500 for dilution #5 and 1:312,000 for dilution #6. (3)
It is not unusual to find tests with a combination of results where the patient exhibits reactivity to some allergens that require a weak concentration of allergen and to some allergens that require a strong concentration of the allergen. Positive test results during an IDT more frequently occur with strong allergenic concentrations (dilutions #3, #2 or #1).
According to traditional teaching it is rare to find an allergen that reacts to dilution #6. (4) In agreement with that statement, prior to 2012 it was rare to find a patient that showed reactivity to the 6th dilution during skin testing. Since late 2012, it became increasingly frequent to find patients that exhibited positive skin responses to very weak allergenic concentration, like the 5th and even to the 6th dilutions.
* Many positive results. It would have been rare before 2012 to find a patient that reacted to most of the allergens in the tested panel. Since that time, it was not uncommon to find patients that react to many or even all tested allergens.
Skin Reactivity and General Health in the Post-Hurricane Population
The findings in the two reports mentioned above (1,2) suggested not only that post-hurricane patients were more reactive (skin tests had a larger number of positive results, with more tests being reactive to very diluted allergen) but also that the general population after the hurricanes was more affected with earlier onset of symptoms and with more severe symptoms as suggested by a lower age average: more patients younger than 18 years of age and more patients with asthma or lower respiratory symptoms (LRS).
The patient charts were randomly selected and were not necessarily the same for both reviews. Yet, both reviews showed similar results, which again suggests a change in the health of the local population.
Mold Skin Reactivity During Skin Testing
Molds allergens are characteristically not as reactive in the skin as pollen allergens, for example. It was not unusual prior to the hurricanes to use the 3rd or even 2nd dilutions (carrying strong allergenic concentration) as the first injection when testing molds with IDT in healthy patients. After 2012, molds became more reactive. Many more molds were positive in the allergy test, and results occurred at much weaker allergenic concentration (4th, 5th or even 6th dilutions). Molds did not elicit large wheals as it was observed for the other allergens. (1) The overall number of positive mold skin test results before the hurricanes was 285 versus 987 after the hurricanes. (2)
Before the hurricanes, 97% of the positive results required a strong allergenic concentration (dilutions #3, #2 or #1). After the hurricanes, only 75% of the results did so (p<0.0001). The decrease in the percentage value occurred despite the overall increase in the number of positive results because of the large increase in the number of positive reactions occurring with weak allergenic concentration after the hurricanes.
Of note is that many of the 97% of the positive results before the hurricanes or the 75% of the positive results after the hurricanes that required strong allergenic concentration would have been missed if only a 1:1000 wt/vol dilution of the mold allergens was used. (5)
With the Intradermal Dilutional Test, dilution #2 has an allergenic concentration of 1:500 wt/vol and dilution #3 a concentration of 1:2500 wt/vol. A single injection of allergen with a concentration of 1:1000 wt/vol as advised by the guidelines of the main allergy society is an intermediate concentration between the second and third dilutions of the IDT, and it would miss many of the positive results obtained by the IDT. This can explain the perception in main allergy communities that the role of mold in allergic disease is negligible. (5,6)
This perception is understandable as molds are usually missed by skin prick tests (SPT), and they can frequently be missed by an intradermal test with a 1:1000 wt/vol dilution. (3) The IDT can demonstrate reactivity to allergens that appear to be not reactive with the SPT (7) or with an intradermal injection of a fixed allergenic dose. This is more important when considering mold allergens because they are, as explained above, not very reactive in the skin.
The increase in the number of positive results with weak allergenic concentration after the hurricanes (p<0.0001) strongly suggests that the skin reactivity for mold allergens has greatly increased in our patients after the hurricanes. This is further suggested by the following findings:
a) Before the hurricanes, 38% of the charts showed no reactivity to any of the 18 molds sampled. After the hurricanes, this occurred only in 5% of the cases.
b) Before the hurricanes, no chart was found where the patient reacted to all of the 18 tested molds. After the hurricanes, this happened in 17% of the sample.
Relevance of Lower Respiratory Symptoms
In a chart review done to validate the use of a Peak Flow Meter (PFM) device as an adjuvant for the management of allergy patients, (8) it was observed that a large majority of the patients that denied having asthma had symptoms pertaining to the lower airway like shortness of breath, exercise-triggered symptoms, history of inhaler use, or abnormal spirometries.
In that paper it was established that the PFM was a useful device in the management of allergic patients, as the peak flow value improved if immunotherapy was successful (predictor value of 91%), but it also suggested that simply asking "Do you have asthma?" is not enough to determine if a patient has potential lower airway reactivity. It became obvious that patients with symptoms pertaining to the lower airway could be more reactive than patients without symptoms suggestive of inflammation of the lower airway. Taking this into consideration can help decrease the chances of triggering a reaction during testing or treatment. It is our opinion that a patient with lower respiratory symptoms (LRS) should be on an inhaled corticosteroid during the time that testing is being done and probably for the first few months of immunotherapy.
About Flooded and Damp Environments
Floods after hurricanes provide a propitious environment for mold growth. Buildings that remain wet for 48-72 hours following hurricanes or floods frequently develop visible and extensive mold growth. (9)
We have often observed that patients reported becoming allergic or experiencing a worsening of their preexistent allergies after their homes flooded during those hurricanes. Home water damage can also occur after leakage from water or sewage pipes, but these water intrusions do not affect a massive segment of the general population as it happens with hurricanes or floods. The flooding that followed hurricanes Irene and Sandy was significant. It makes logical clinical sense to infer that the environmental changes following those storms affected the local population.
A unique aspect of our studies is that because we had access to both pre- and post-hurricane charts, the comparison included the same local population both before and after the climatic events.
Impact of These Findings for Patient Management
Changing testing protocol. The concept of the IDT is based on starting the test with a weak dilution of the allergen, considered safe to inject in the patient being tested. (10) If this dilution is non-reactive, the test continues by injecting a more powerful dilution; and this process continues until determining reactivity to the allergen being tested (or lack of).
In the years before the hurricanes, it was so rare to see a patient reacting at the 6th dilution, that unless the patient was asthmatic, testing usually started for most allergens with the 4th dilution. (4)
Since the hurricanes, most tests are now started with the weakest 6th dilution. Even with this precaution, some reactions have been encountered upon injecting the 6th dilution as the initial dose. This had never occurred before 2012.
Use of inhaled corticosteroids. The number of patients with asthma or with LRS has markedly increased since the hurricanes. These patients have lower airway inflammation. A frequently encountered example is shortness of breath with exertion. Often these LRS have developed no more than a few years before consultation. Even though many patients explain that the problem is related to their lack of exercise, their smoking, or their being overweight, it is a common finding that the symptoms improve after two to three weeks of administering an inhaled cortico-steroid (ICS). Administering ICS to patients with LRS, starting two to three weeks before testing date, probably helps decrease the chance of triggering a reaction involving the lower airway during testing. A good history is now more important than ever to decide if and when to test an allergic patient with LRS.
Number of allergens tested in one session. Instead of testing all allergens in one session, we now divide the IDT panel in smaller sub-panels for patients with LRS. Having a smaller number of injections per session decreases the chance of triggering a reaction during testing.
Co-seasonal testing. Before the storms, it was not unusual to test well-controlled asthmatic patients in season (such as ragweed in July-August). Since the hurricanes, in season testing of patients with LRS is avoided. -
The general patient population in our geographical area has been found, from the clinical point of view, to be more reactive since exposure to the hurricanes of 2011 and 2012.
This is suggested by the larger number of patients presenting with symptoms suggestive of lower airway inflammation and larger number of younger patients presenting with allergic symptoms and was confirmed by the overall increased sensitivity with increased reactivity during testing.
Extra precautions have been incorporated in clinical practice to manage these patients.
After the hurricanes many patients developed allergies, with or without asthma, or experienced worsening of preexistent allergies with or without asthma. Some patients reported having had asthma during childhood and having been well controlled until after the hurricanes. Home water intrusion after the hurricanes has been described. Without addressing the significance of home remediation or the lack of awareness in the general population of the significance of a damp environment, it is clear that a change in the general population of the affected geographical area has occurred.
There has been flooding after hurricanes in other geographical areas. The better studied example is, perhaps, the effects of Hurricane Katrina over the New Orleans area. Published reports show confusing results that prevent clear conclusions. For example, it was reported that symptoms were significantly higher in children exposed to below-median levels of indoor airborne mold, that no relationships were observed between skin sensitivity and indoor or outdoor allergen concentrations, and that asthma symptoms were not influenced by allergen concentration/sensitivity, (11) or that while upper and lower respiratory symptoms were higher after the hurricane, mold growth at home was associated with lower respiratory symptoms. (12)
It has been proposed that the difficulty interpreting the studies on health effects of indoor mold exposure is related to the perception that mold is associated with few serious adverse effects in healthy people, that relocation of affected individuals led to avoidance of exposure to mold, and that the lack of access to health centers prevented cases from being recorded. (13)
The potential role of mold in the development and exacerbation of respiratory disease is still not part of basic accepted medical knowledge, even though it has been found that exposure to damp-moldy indoor spaces is associated with cough, wheezing, and lower respiratory illness. (14)
Below are examples of how data can become confusing:
* A report described that the respiratory symptoms with dry cough called "Katrina cough" were believed to be caused by reactions to mold and dust left after the storm. (15) The same report concluded that the respiratory conditions were not severe enough and that the consultations at emergency rooms in New Orleans were similar to the national data. (15)
* A study claimed that dust and sediment from Hurricane Katrina did not cause an increase in severe respiratory problems for people living in the Greater New Orleans area. (16) It further stated that the rates of respiratory illness were not different from the rates of these illnesses occurring in other parts of the state and the country and also that "there is no such thing as a single condition such as 'Katrina Cough' that would be different from the bacterial and viral respiratory conditions we would expect to see at that time of year." (16)
* Another study concluded that there was no increased incidence of upper or lower respiratory tract symptoms from before and after Katrina. (17) In this particular study the subjects were recruited from an area of the city that did not flood; the majority of homes had minor or no water damage, and from those that did, half of them had been repaired before the study began. The negative findings of this study are not surprising.
* A group of people was evaluated after their homes were damaged by Hurricane Katrina. (6) Despite significant home damage and evidence of extensive exposure to dampness and mold, no relationship between that exposure and sensitivity to mold allergens was encountered. The authors concluded that, in agreement with previous literature, there was no excess risk of respiratory symptoms. The subjects in this (6) and other studies (11) were tested with SPTs. When considering that SPTs are not sensitive (18) and that only the IDT is able to diagnose patients that exhibit reactivity to strong allergenic concentration, (3) the reported results and subsequent conclusions are not unexpected.
In the 12 years prior to Katrina, children from the local population had a sensitization rate to fungi of 59% to 66% (19) which increased to 75% after the Hurricane. (20 ) This is, at best, a modest increase. It appears that a large percentage of the children of the area affected by Katrina were already reactive to mold. This could be an underlying problem: The area that was eventually affected by Hurricane Katrina is known to have an endemic rate of asthma that reaches epidemic proportions, (21) so the influence of a natural disaster perhaps did not become clear as this was already a heavily affected area with a high prevalence of sensitization to mold and to other allergens.
Planning an epidemiological study is at best extremely difficult and complicated. Relying on tests that are not accurate will obviously lead to wrong conclusions. Evaluating the population itself might be more revealing than evaluating test results or dust samples. A sick person is a sick person even if the air samples do not show what is usually assumed to be a dangerous level of particulate matter. A survey where patients are asked how their health is at the time of the survey compared to before the natural disaster might perhaps be more helpful in establishing a change in the health of the general population. More important than measuring how much dust is in a home or what is the concentration of specific allergens or other toxic substances, it is to determine if the inhabitants from that home are symptomatic or not. A sensitive individual will react to a lower allergenic concentration. The fact that it has been "proven" that a certain population did not develop asthma with a certain allergen concentration in a prior study does not mean that another population will not be affected by that supposedly low level of allergen, so measuring allergen concentration rather than evaluating the health of the local population may lead into erroneous conclusions.
Are the observations discussed in this report also occurring in other areas of the country affected by flooding or hurricanes, and if they are, how are those patients handled? The answer to this obvious question is difficult.
Because most patients are studied with tests of poor diagnostic power, it is not surprising that many people live their lives affected with symptoms, frequently severe enough to impact on their quality of life. Reactivity to mold or to other inhalant allergens is frequently not demonstrated or incompletely demonstrated. Adding to this fact, the usual lack of awareness of the potential adverse effects on health due to mold exposure helps to explain why intervention is usually not implemented.
Well-referenced information about the real implications of a natural disaster is available. (22) That information helps to explain why the published reports offer confusing information. The fact that mold develops after a flood (and toxins and other irritants accumulate) becomes easy to understand. It is logical to assume that similar problems will develop in other similarly affected areas. (22) Compared with the real consequences of mold exposure, (22,23) our report is just like "the tip of the iceberg": we learned that the skin reactivity has changed and that patients appear to be sicker. People exposed to mold from floods or other forms of water intrusion, indeed, become extremely sick with a much more significant array of problems than allergies.
(1.) Saporta D. Changes in Skin Allergy Testing Reactivity observed after a Hurricane. Is the Environment Responsible? SOJ Immunol. 2015:3(3): 1-6.
(2.) Saporta D, Hurst D. Increased Sensitization to Mold Allergens Measured by Intradermal Skin Testing following Hurricanes. Journal of Environmental and Public Health. 2017. Article ID 2793820.
(3.) Saporta D, Hurst D. Management of the allergic patient. The role of different diagnostic tests. Townsend Letter. April 2018;52-S5.
(4.) Fornadley JA. "Skin testing in the diagnosis of inhalant allergy," in Allergy and Immunology, an Otolaryngic Approach. J. H. Krouse, et al, Eds. Philadelphia, PA: Lippincott Williams & Wilkins: 2002: 114-123.
(5.) Bernstein L, et al. Allergy Diagnostic Testing: An Updated Practice Parameter. Annals of Allergy, Asthma, & Immunology. 2008;100(3): S3.
(6.) Rabito FA, et al. The Relationship between Mold Exposure and Allergic Response in Post-Katrina New Orleans. J Allergy (Cairo). 2010; pii: 510380.
(7.) Simons JP, et al. Comparison of Multi-Test II skin prick testing to intradermal dilutional testing. Otolaryngol Head Neck Surg. 2004;130(5):536-544.
(8.) Saporta D. Changes in Peak Flow Meter Values During Immunotherapy Administration. Journal of Environmental and Public Health. Volume 2012, Article ID 212867.
(9.) Brandt M, et al. Mold prevention strategies and possible health effects in the aftermath of hurricanes and major floods. MMWR. Recommendations and Reports. 2006;55(RR-8): 1-27.
(10.) King HC, Mabry RL, Mabry CS. Allergy in ENT Practice. New York: Thieme; 1998: p. 118.
(11.) Grimsley LF, et al., Few Associations Found Between Mold and Other Allergen Concentrations in the Home versus Skin Sensitivity from Children with Asthma after Hurricane Katrina in the Head-Off Environmental Asthma in Louisiana Study. International Journal of Pediatrics. 2012;Article ID 427358.
(12.) Rath B, et al. Adverse Respiratory Symptoms and Environmental Exposures Among Children and Adolescents Following Hurricane Katrina. Public Health Rep. 2011 Nov-Dec; 126(6): 853-860.
(13.) Barbeau DN, et al. Mold exposure and health effects following hurricanes Katrina and Rita. Annual Review of Public Health. 2010;31(1):165-178.
(14.) Inst. Med. Comm. Damp Indoor Spaces Health. 2004. Damp Indoor Spaces and Health. Washington, DC: Natl. Acad. Sci.
(15.) http://new.dhh.louisiana.gov/assets/oph/Center-PHCH/Center-CH/stepi/specialstudies/Katri naCoughReport.pdf
(17.) Rabito FA, et al. Children's respiratory health and mold levels n New Orleans after Katrina: a preliminary look. J. Allergy Clin. Immunol. 2008;121:622-25.
(18.) www.worldallergy.org/UserFiles/file/WhiteBook2-2013-v8. pdf. (page 111)
(19.) Kim LR, El-Dahr JM. Skin test reactivity in children with asthma and rhinitis in New Orleans prior to Hurricane Katrina. J Allergy Clin Immunol. 2006;117(2):S6.
(20.) El-Dahr JM, et al. HEAL-ing New Orleans: the post-Katrina pediatric asthma study (abstract). J Allergy Clin Immunol. 2008;121:S232.
(21.) Salvaggio J, Seabury J, Schoenhardt EA. New Orleans asthma v. Relationship between Charity Hospital asthma admission rates, semiquantitative pollen and fungal spore counts, and total particulate aerometric sampling data. J Allergy Clin Immunol. 1971;48(2):96-114.
(22.) MOLD: The War Within by Kurt and Lee Ann Billings. Kodak, Tennessee; Partners Publishing LLC. 2013.
(23.) Surviving Mold: Life in the Era of Dangerous Buildings by Ritchie C. Shoemaker. Baltimore, Maryland; Otter Bay Books. 2010.
by Diego Saporta, MD, and David Hurst, MD, PhD
Dr. Saporta completed his training in 1990 at Columbia Presbyterian Hospital in New York City. He is board certified in otolaryngology and has been a fellow of the American Academy of Otolaryngic Allergy (AAOA) since 2001. His private practice in Elizabeth, New Jersey, is heavily oriented to the management of allergic conditions. Interested in the use of oral vaccines since early in his practice, Dr. Saporta presented a protocol for sublingual immunotherapy at the 64th annual meeting of the AAOA that since then has been successfully used for the management of allergic rhinitis with or without asthma.
David Hurst, MD, PhD is a clinical instructor in otolaryngology at Tufts University in Gorham, Maine.
|Printer friendly Cite/link Email Feedback|
|Author:||Saporta, Diego; Hurst, David|
|Date:||May 1, 2018|
|Previous Article:||Berberine: New Research on Mechanisms Via Which This Alkaloid May Impact Metabolic and Cardiovascular Health.|
|Next Article:||The Nature of Information and the Metaphysics of Science.|