The guidelines developed by the New York State Workers Compensation Board are intended to assist healthcare professionals in conducting diagnostic testing for asthma.
Tailored for medical practitioners, these Workers Compensation Board guidelines offer support in determining the appropriate diagnostic tests for individuals suspected of having asthma.
It’s important to emphasize that these guidelines do not replace clinical judgment or professional experience. The decision on diagnostic testing for asthma should be a collaborative one, involving the patient and their healthcare provider in consultation.
Spirometry in Work-Related Asthma
Spirometry testing is a crucial element in the assessment and management of individuals with suspected work-related asthma. Spirometry, with or without bronchodilator administration, serves four distinct roles in cases of work-related asthma concern:
- Determining the presence of asthma.
- Excluding other conditions resembling asthma.
- Informing whether the identified asthma is work-related.
- Monitoring the response to therapy and potential return to work.
Recommended Initial Evaluation Method
Spirometry is recommended as an initial evaluation method for diagnosing work-related asthma.
Spirometry with Bronchodilator Response Testing
Essential Test for Pulmonary Function Evaluation
Spirometry with bronchodilator response testing is crucial for assessing pulmonary function and is typically performed in most cases. Variability in airflow obstruction is a fundamental characteristic distinguishing asthma from other obstructive disorders.
Rationale for Recommendation
Indications for spirometry, with or without bronchodilator, in the evaluation of work-related asthma include signs and symptoms consistent with a work-related asthma history.
Purpose of Spirometry with Bronchodilator
The primary use of spirometry with bronchodilator is to document and quantify airflow obstruction. The forced expiratory volume in one second (FEV1) and the FEV1/forced vital capacity (FEV1/FVC) ratio are particularly useful for this purpose.
Confirming Asthma
Asthma confirmation involves demonstrating airflow obstruction through a reduction in both the FEV1/FVC ratio and FEV1, or through a positive metacholine challenge. Repeated spirometry or spirometry followed by repeated peak flow measurements is employed to show that the obstruction is present and variable rather than fixed.
Important Caveats
Use of Serial Measurements
Serial measurements, when correlated clinically, can be employed to track progression and variability under different conditions and exposures. It’s important to understand that improvements in measurements may not always align well with improvements in the disease.
Airflow Obstruction as an Indicator
As asthma is characterized by variability, airflow obstruction serves as an indicator of the status at a specific time. It may not necessarily reflect trends over time, but a much worse FEV1 measurement than a previous one can indicate a deterioration in the disease. Therefore, its primary value lies in demonstrating variability and ruling out irreversible obstruction.
Measurements of Greatest Utility in Spirometry
Forced Expiratory Volume in One Second (FEV1)
FEV1, expressed in liters or as a percentage of predicted values.
Pre/Post FEV1 with Bronchodilator
FEV1 measured before and after (pre/post) administration of a bronchodilator, typically albuterol (salbutamol).
Pre/Post FEV1 for Work Shifts
Measurement of FEV1 before and after (pre/post) a work shift, considering diurnal variation.
Ratio of FEV1 to Forced Vital Capacity (FEV1/FVC)
Expressed as a percentage, this ratio is crucial in evaluating airways disease.
Peak Expiratory Flow (PEF)
Expressed primarily in liters per minute, PEF is particularly useful in monitoring workers with demonstrated reactive airways.
Forced Expiratory Flow Rate (FEF25-75)
Of less central importance, FEF25-75 represents the volume expired between 25% of FVC and 75% of FVC, often referred to as midflows.
Methods
Dependence on Accuracy
Accurate results hinge on the proper use of equipment, adherence to correct test procedures, and qualified interpretation.
Spirometry Testing
Spirometry can be conducted either independently or in conjunction with pre- and post-bronchodilator testing.
Pre- and Post-Bronchodilator Testing
This involves establishing baseline airflow and then assessing whether volumes increase after the administration of a bronchodilating agent.
Reversibility Criteria
As defined by the American Thoracic Society (ATS), a 12% improvement in FEV1 or an absolute value increase of at least 200 mL post-bronchodilator indicates reversibility of airflow obstruction in FVC or FEV1 values.
Paradoxical Responses
In rare cases, subjects may exhibit a paradoxical response to bronchodilators, leading to increased obstruction. This transient effect is associated with highly reactive airways responding to a nonspecific stimulus, displaying a slow response to the agent.
Changes in Peak Flow
While changes in peak flow are expected and used for monitoring treatment progress, they are not employed for diagnostic purposes.
Interpretation of Spirometry
Limitations in Differentiation
Spirometry, with or without bronchodilator, cannot distinguish occupational asthma from non-occupational asthma and should be interpreted alongside additional information from history or supplementary testing.
Relevance of Single Test Day
A failure to demonstrate reversible airway obstruction on a single test day does not rule out the diagnosis of asthma or general airways reactivity.
Published Guidelines
The American Thoracic Society and European Respiratory Society (ATS/ERS) have issued statements outlining how to conduct and interpret spirometry. Additionally, OSHA has recently provided guidance on best practices for occupational spirometry testing.
Peak Expiratory Flow Rates (PEFR)
Definition
PEFR is defined as the maximum flow achieved during forceful expiration, initiated from the point of maximum inspiration, using simple portable meters. Serial PEFR measurements track the circadian rhythm, displaying lower values in the early morning and peaking in the afternoon, with more significant variations in individuals with bronchial asthma.
Patient-Performed PEFR
PEFR must be conducted by the patient outside of a medical setting to be valuable in evaluating occupational asthma. It can be easily obtained at and away from work to document changes in flow potentially linked to the workplace environment or exposures.
Peak Expiratory Flow Rates – Serial Measures
Recommended Usage
Serial PEFR is recommended for confirming a diagnosis of work-related asthma in patients already diagnosed through other methods. Patients should be trained by a physician or qualified staff on the proper use of the meter and the importance of accurate recordings.
Indications
Serial PEFR is indicated to screen patients with a history consistent with work-related asthma (WRA).
Rationale for Recommendation
Serial PEFR is recommended as an initial method for investigating suspected occupational asthma (OA) and WRA. Initiating serial PEFR early in the evaluation, when patients are likely still exposed to a potential cause of asthma, is desirable. These measures provide information on airway resistance both at work and at home.
Method
Assessing serial measurements of PEFR at and away from work confirms the relationship between exposure and bronchoconstriction. Standards for PEFR devices and their performance have been published by ATS and the subcommittee on Occupational Allergy of the European Academy of Allergy and Clinical Immunology group, with recommendations for the total duration and frequency of measurements. Workers are typically instructed to record PEFR every two to three hours for four weeks, including periods at and away from work. Diary cards, available at www.occupationalasthma.com, can be used to record activities and symptoms, including bronchodilator use.
Recording and Analysis
Each measurement session should include three or more forced expiratory maneuvers, with the best attempt recorded. The best of three PEFR readings should be recorded if the best two readings were within 20 L/minute of each other. A recording period of four weeks, including at least two weeks away from suspect exposure, is recommended. PEFR measures should be obtained at awakening, mid-day, end of the shift, and before bedtime. Some investigators recommend measurements every two hours while awake. The use of a freely downloadable automated data plotting and analysis system, available at www.occupationalasthma.com, may reduce human variability in interpreting PEF values.
Advantages and Limitations
Advantages
PEFR can offer objective evidence of the relationship between work and asthma worsening.
Limitations
PEFR is heavily dependent on the worker’s efforts, including reliable performance of a forced expiratory maneuver and accurate recording of results. It cannot differentiate between occupational asthma (OA) and work-exacerbated asthma.
Non-Specific Bronchial Provocation Test
Purpose and Usage
Bronchoprovocation tests using methacholine, histamine, cold air, or exercise challenges play a crucial role in diagnosing asthma, especially when there’s suspicion and spirometry results are normal or nearly normal. Among these, methacholine and histamine challenges are the most commonly employed, with methacholine being preferred due to fewer side effects and increased reproducibility in lung function measurements.
Reflecting Airway Sensitivity
Non-specific bronchial provocation testing is believed to reflect the heightened sensitivity of airways to inhaled nonspecific stimuli or irritants, often reported by asthma patients. These stimuli are thought to induce airflow limitation primarily through an impact on airway smooth muscle, albeit with varying preceding mechanisms. While increased methacholine reactivity may resolve a few months after exposure, it has been demonstrated to persist for more than 13 years post-exposure.
Method
Inhaling Pharmacologic Stimuli
There are two methods for inhaling aqueous solutions of pharmacologic stimuli: the 2-minute tidal breathing protocol and the 5-breath dosimeter protocol. The process begins by measuring baseline lung function and calculating a target FEV1 indicating a 20% fall in FEV1. Optional inhalation of a placebo or diluent (0.9% NaCl) is considered. Methacholine inhalation typically starts at concentrations of 0.031 to 0.0625 mg/mL, doubling or quadrupling up to 16, 25, or 32 mg/mL based on the protocol. The FEV1 is measured after each inhalation, and the test concludes when the FEV1 falls by 20% from baseline or diluent value. The response is expressed as a provocative concentration (PC20) producing a 20% fall in forced expiratory volume in 1 second. The presence of asthma is usually defined as a ≥20% fall in the FEV1 at a methacholine dose of 4 mg/mL or below. Methacholine doses from 4-16 mg/mL are considered borderline for categorizing bronchial responsiveness based on the PC20 mg/mL dose.
Recommended Usage
The test is recommended for diagnosing asthma if the clinical history is compelling, and other diagnostic tests such as spirometry and bronchodilator responsiveness do not provide conclusive results.
Criteria and Standards for Use
Bronchial challenge testing should adhere to the guidelines outlined in the 1999 ATS statement and the 1993 European Respiratory Society statement (updated in 2008) source.
Indications/Contraindications
Bronchoprovocation using methacholine or cold air is a viable method for establishing an asthma diagnosis, especially when there is suspicion and spirometry yields normal or near-normal results. However, nonspecific bronchial provocation (NSBP) is generally not recommended if the baseline FEV1 is <65% of predicted.
Absolute Contraindications for Methacholine Challenge Testing
- Severe airflow limitation (FEV1<50% predicted or <1.0L), heart attack, or stroke in the previous three months.
- Uncontrolled hypertension (systolic BP>200 or diastolic BP>100).
- Known aortic aneurysm.
Relative Contraindications for Methacholine Challenge Testing
- Moderate airflow limitation (FEV1 <60% predicted or <1.5L).
- Inability to perform acceptable-quality spirometry.
- Pregnancy.
- Nursing mothers.
- Current use of cholinesterase inhibitor medication (for myasthenia gravis).
Mannitol Bronchial Provocation Test
Not Recommended for Diagnosing Work-Related Asthma
The Mannitol Bronchial Provocation Test is not recommended for use in diagnosing work-related asthma. Additional steps are necessary to establish the work-relatedness of asthma.
Evidence for the Use of Nonspecific Bronchial Provocation Test
Specific Immunological Testing
Specific immunological testing for suspected allergens is commonly employed to assist in diagnosing allergic rhinitis and occupational asthma. These tests aim to assess type I (IgE) hypersensitivity reactions to specific allergens and can be valuable in diagnosing cases of occupational asthma caused by immune or allergic mechanisms, as opposed to irritant-induced asthma. However, the presence of specific antibodies indicates an immune response but does not necessarily establish a causal relationship with occupational asthmatic symptoms. Therefore, demonstrating sensitization to an occupational agent through specific IgE and/or skin testing alone, without confirming the work-relatedness of asthma, is insufficient for an occupational asthma diagnosis.
Detection Methods for IgE
Detection of IgE to a specific allergen is achieved through skin prick testing (SPT) and serum IgE testing when kits are available for the specific allergen. Three methods for detecting serum IgE antibodies have been utilized to assess antigenicity to occupational antigens: RAST, ELISA, and ImmunoCAP.
Classification of Sensitizing Agents
The sensitizing agents known to induce occupational asthma are traditionally categorized into high molecular weight (HMW) and low molecular weight (LWM) antigens.
IgE Specific Immunological Testing for High Molecular Weight Specific Antigens
Recommended for Workers with Symptoms of Occupational Asthma
For workers exhibiting symptoms consistent with occupational asthma related to certain high molecular weight specific allergens, IgE specific immunological testing is recommended. This is particularly applicable when standardized antigens and assay protocols are available. High molecular weight allergens, supported by quality studies, include flour dusts, bovine danders, laboratory, and other animal allergens. Serum IgE testing can confirm natural rubber latex (NRL) allergy, but it may not cover all potential NRL allergens, meaning a negative result does not necessarily exclude the diagnosis of NRL allergy.
IgG Specific Immunological Testing for High Molecular Weight Specific Antigens
Not Recommended as a Diagnostic Tool
IgG specific immunological testing for high molecular weight specific allergens is not recommended as a diagnostic tool for select workers exhibiting symptoms consistent with occupational asthma related to high molecular weight specific allergens.
Low Molecular Weight Agents
Low molecular weight agents become allergenic only after binding with one or more autologous serum, epithelial, or tissue proteins. Common low molecular weight agents include diisocyanates, colophony fume liberated from cored solder in the electronics industry, complex platinum salts, and the family of acid anhydrides found in the manufacturing of resins.
IgE Specific Immunological Testing for Low Molecular Weight Specific Antigens
Not Recommended for Workers with Symptoms of Occupational Asthma
IgE specific immunological testing for low molecular weight specific allergens is not recommended for workers exhibiting symptoms consistent with occupational asthma related to low molecular weight specific allergens. The majority of low molecular weight antigens lack validated commercial assays for specific antibody testing.
Method
This type of testing should only be used for allergens that have demonstrated acceptable sensitivity, specificity, positive predictive value, and negative predictive value through a validated method in investigational studies.
Advantages and Limitations
Not all cases of occupational asthma are believed to involve IgE and/or IgG-mediated immune responses. Data suggest that IgE is involved in subsets of symptomatically exposed workers, especially to high molecular weight antigens.
Skin Prick Testing
Skin tests are utilized alongside a directed history and physical examination to confirm or exclude sensitization in IgE-mediated diseases, including asthma. In clinical practice, two types of skin testing are employed: percutaneous testing (prick or puncture) and intracutaneous testing (intradermal). When local tissue mast cells possess surface IgE specific to the tested allergen, the cross-linking of IgE triggers the release of preformed histamine from mast cells, resulting in increased vascular permeability and the formation of a wheal. Inflammatory mediators initiate a neural reflex, causing vasodilation and erythema (the flare). Test results typically include the size of the wheal and flare in millimeters, presented as W/F mm/mm, and compared to the negative saline control response. Alternatively, results may be reported on a 0 to 4+ scale, with 1+ indicating erythema smaller than a nickel, 3+ denoting wheal and erythema, and 4+ indicating a wheal with pseudopods and erythema.
Most literature suggests that when a skin prick test result is negative, a positive intradermal skin test (IDST) result contributes minimally to the diagnostic assessment of inhalant allergy. IDST is warranted and should be selectively employed in cases with a compatible or compelling history and a negative or equivocal skin prick test (SPT) result. Numerous studies have demonstrated a stronger correlation between the prick skin test response and clinical allergy.
Skin prick testing has been applied to assess allergy to asthmagens across various patient types and occupational settings. Workers should be directed to a physician experienced in skin prick testing for interpretation to evaluate atopy and identify potential causative allergens. The testing process should be conducted by trained and qualified personnel under the supervision and interpretation of a physician with expertise in the technique.
Skin Prick Testing to High Molecular Weight Allergens
Recommended – For specific individuals experiencing symptoms indicative of occupational asthma to particular allergens, especially when validated, commercial skin testing extracts are accessible. High molecular weight allergens with ample evidence supporting their use include natural rubber latex, wheat and rye flour, grain dust, alpha-amylase, bovine danders, as well as laboratory and other animal allergens.
Skin Prick Testing to Low Molecular Weight Allergens
Recommended – For specific individuals with symptoms consistent with occupational asthma related to particular allergens, and when skin testing extracts are obtainable. Low molecular weight allergens with sufficient evidence supporting their use include reactive dyes, halogenated platinum salts, and trimellitic anhydride.
Skin Prick Testing to Other Allergens Not Covered Above
Not Recommended – For allergens not mentioned previously. When specific allergens lack evaluation in quality studies reporting specificity and sensitivity, skin prick testing for these allergens cannot be recommended. Additionally, skin prick testing is not advised if the suspected cause is non-allergenic.
Rationale for Recommendations
Various studies incorporate skin prick testing as part of the diagnostic protocol, although it is often regarded as a test for atopy rather than a diagnostic tool for occupational asthma.
Method
The performance of skin prick testing is addressed in a practice guideline by the American Academy of Allergy, Asthma & Immunology (AAAAI) and the American College of Allergy, Asthma & Immunology (ACAAI).
Indications
Prick skin testing should be conducted with allergens demonstrating acceptable sensitivity, specificity, positive predictive value, and negative predictive value. Allergens associated with occupational asthma meeting these criteria include natural rubber latex, wheat and rye flour, grain dust, alpha-amylase, reactive dyes, bovine danders, laboratory and other animal allergens, halogenated platinum salts, and trimellitic anhydride.
Harms
There is a rare risk of severe asthmatic or anaphylactic reactions associated with skin prick testing.
Advantages and Limitations
The risk of fatality due to skin prick testing is extremely remote, and severe/anaphylactic reactions are rare. However, this risk cannot be completely ruled out in highly susceptible subjects, such as those with a history of previous anaphylactic reactions, pregnant women, individuals with uncontrolled asthma, or those with a high degree of reactivity. Skin testing should be avoided in pregnant women and limited to other high-risk individuals where the consequence of the result outweighs the risk.
Specific Inhalation Challenge
Overview: Specific Inhalation Challenge (SIC), also known as Specific Bronchial Provocation Test (SBPT), involves exposing an individual to a suspected asthmagen under conditions simulating the workplace. The subject’s lung function is then monitored for an asthmatic response. SIC is employed when other diagnostic methods fail, serving as a reference standard due to the absence of an alternative definitive test.
Recommendation: Recommended – SIC is advised for diagnosing work-related asthma in highly specific cases, especially when the diagnosis is strongly suspected but hasn’t been established through less invasive methods. The testing should occur in appropriately equipped facilities with continuous medical supervision.
Method: The test may have serious complications, including fatalities. Only a few centers equipped with proper facilities can safely and accurately perform these tests. Asthmagen exposure is conducted after a control day without exposure to the suspected sensitizer, and lung function stability is monitored. Positive responses, defined as a 20% fall in FEV1, may exhibit an immediate or delayed pattern, depending on the nature of the agents.
Indications: SIC is indicated for the evaluation of a worker who left the workplace and cannot or will not return, initial documentation of a new cause of occupational asthma, identification of a specific causative agent in the presence of multiple substances, and confirmation of the diagnosis when other methods are not feasible or have failed.
Harms: Potential harms include excessive bronchoconstriction, asthma exacerbation, and infrequently systemic and anaphylactic reactions.
Advantages and Limitations: SIC is not considered necessary in cases where work-related airway obstruction is confirmed, or the worker is sensitized to a known causative agent. Limitations include challenges in replicating work exposure, cases involving a mixture of agents, loss of immediate reactivity due to prolonged absence from exposure, and variations in airflow unrelated to exposure in individuals with unstable asthma.
Rationale for Recommendation: SIC is recommended for highly specific cases where an accurate diagnosis is crucial.
Nitric Oxide (Fractional Exhaled Nitric Oxide, FENO)
Overview: The measurement of total exhaled nitric oxide (FENO) serves as a test for detecting endogenous inflammatory signals, particularly in asthma. FENO is recognized for assessing pathological changes associated with asthma, reflecting eosinophilic inflammation. Various factors, such as smoking, inhaled steroid use, exercise, height, gender, atopy, recent pulmonary infections, ambient air NO levels, and other pulmonary function tests, may influence FENO results, making comparisons challenging.
Recommendation for General Use: Recommended – FENO testing is advised for the selective assessment of individuals with moderate to severe asthma to monitor treatment and control. Strict protocols and a clear understanding of the test by both the examiner and interpreting clinician are essential.
Diagnosis of Asthma: Recommended – Exhaled nitric oxide testing is recommended for establishing an asthma diagnosis in specific cases where additional evidence is needed for confirmation, especially when pulmonary function tests or provocation tests are nondiagnostic.
Selective Monitoring of Asthma: Recommended – FENO testing is recommended for selective use in monitoring airway inflammation in patients with moderate or severe asthma. This becomes particularly useful when biologicals are employed in asthma treatment.
Criteria and Standards for Use: Utilize criteria and standards outlined in the ATS 2011 statement for the Interpretation of Exhaled Nitric Oxide Levels for Clinical Applications.
