The following paragraphs are not an admission that anything discussed in them is prior art or part of the knowledge of persons skilled in the art.
Allergy results when an allergic patient is exposed to an allergen for which they are sensitized. In the allergic individual, this may lead to early and late phase responses, which result in localized and systemic inflammation, and ultimately the allergy signs and symptoms of rhinitis and conjunctivitis are typical. The common nasal symptoms of rhinitis include nasal congestion, itchiness, runny nose and sneezing. The typical ocular symptoms of conjunctivitis include ocular hyperemia, itching and tearing. These symptoms have been shown to impact the day-to-day quality of life of its sufferers, and are known to have a socioeconomic impact. Allergic asthma is a more serious condition which involves the lower respiratory tract and may result in long-standing lung function disability, and even death.
Globally, allergy prevalence is increasing. Medications that may better address the underlying mechanisms of allergy and asthma are needed. In order to test anti-allergy medications towards approval for marketing, clinical trials need to be performed. The United States Federal Drug Agency (FDA) indicates that drugs approved for allergy need to demonstrate safety and efficacy in the treatment of allergy. This process requires that drugs are tested in three different phases: Phase I, Phase II, and Phase III. In order that drugs are well evaluated, it is important that testing is done in a non-biased fashion and in such a way that drugs are tested on enough patients to be representative of the general allergic population. As the drug progresses through the testing phases, studies become larger and often involve thousands of patients to be studied across many geographic and climatic regions and countries.
In allergy studies, the amount of symptoms that patients' exhibit tends to be directly related to their allergen exposure. There may be variability in the allergen exposure of different patients as allergen exposure is dependent on patient lifestyle, everyday environment, and, in the case of seasonal allergens (such as plant pollens like ragweed pollen), the natural level of allergen released. For seasonal allergens, a patient's allergen exposure may depend on their job type, for example, if they work daily in the office, allergen exposure may be lower than a patient who works as a gardener and is exposed to pollen release daily for long durations. The natural amount of allergen is further affected by climatic conditions, such as barometric pressure, temperature and rainfall. Taken together, there is even greater variability in patient symptoms and may result in difficulty assessing the true effect of drugs across different populations, locations and climates.
Allergen immunotherapy as a regulated therapy is a relatively recent treatment therapy which works to alter the underlying mechanisms of allergy. Since allergen immunotherapy is typically specific for one allergen type, and patients are often poly-allergic to multiple allergens which overlap in their release seasons, this adds to the complexity of immunotherapy testing. Further, perennial allergens, such as dust mite and cat allergens, are persistently released in some allergic patients' homes. Many patients are allergic to both seasonal and perennial allergens. Thus, despite the potential of allergen immunotherapy, the difficulty in assessing the effectiveness of immunotherapy therapy in one allergen type given the potential for variability in exposure poses a barrier to their true testing.
In response to this potential variability amongst patients and their daily allergen exposures during drug testing clinical trials, fixed facilities or allergen exposure rooms have been built in which airborne allergen levels are controlled and airborne allergen exposure to patients is also controlled. Typically, allergic patients who have a history of allergy to a specific allergen and a positive skin prick test to the same allergen are first screened with an allergen challenge in an allergen test facility for adequate symptom levels. This allows for an actual demonstration of allergy symptoms within the facility to be assessed by the patient or the investigator with symptom score cards, as well for various objective tests to be performed while the patients are in-house, such as nasal patency using acoustic rhinometry.
Some facilities accommodate dozens of patients in a theater-like configuration, and thereby allow the simultaneous testing of many patients ensuring consistency of allergen exposure across patients. Patients who are eligible from the screening session in the allergen chamber return to the chamber later, typically after a period of time greater than one week later (after the allergy symptoms have subsided). Patients are again challenged with allergen exposure in the test facility and either tested prophylactically or for treatment effect after symptom development in response to various test medications.
Individual responses and responses on average across a number of patients may be reproducible in the fixed allergen facility. This is an advantage over traditional field trial approaches, where patients are included in the clinical trial on the basis of medical history of allergy and without the actual demonstration of adequate symptoms that may be observed and rated directly within an allergen challenge test system by both the patient and the observer. In general, in a fixed allergen facility, patients are exposed to allergen at levels similar to that encountered on a peak pollen day and result in the provocation of patient allergy symptoms. Drugs which act prophylactically or after symptoms develop may be tested with these facilities.
Fixed allergen exposure facilities have been built to study allergy patients. For example, in 1999, Dr. Piyush Patel created the Environmental Exposure Chamber (EEC) model for study of allergic patients in Mississauga, Canada, and greater than 50 allergy and asthma studies have been conducted in the facility.
Furthermore, International Publication No. WO/2007/140601 discloses a method, materials and apparatus for investigating asthma using dust mite allergen in an environmental exposure chamber, and International Publication No. WO/2010/099625 discloses a method and chamber for exposure to non-allergic rhinitis trigger environments, and the entire contents of each are hereby incorporated herein by reference.
The Center for Biologics Evaluation Research of the FDA in their evaluation and guidelines for allergen specific immunotherapy testing have indicated their openness to consideration of multicenter allergen challenge test center studies. However, there remain difficulties standardizing existing fixed chambers. For example, one facility may be shown to have an allergen tolerance of ±500 pollen grains per cubic meter air, while another may have a tolerance of ±1000 pollen grains within sites within the test chamber. These differences in pollen levels may result in different levels of symptom response in the same patient. Furthermore, the varied proprietary designs of the chambers may preclude harmonization, and could dictate large rebuilds and expenditures even if it were possible to retrofit to provide similar spatial and temporal validation characteristics of allergen exposure to patients.
Introduction
The following paragraphs are intended to introduce the reader to the more detailed description that follows and not to define or limit the claimed subject matter.
In summary then, the research described above may not provide the capability to allow for a mobile allergen test system, which controls consistent levels of naturalistic airborne allergen exposure to patients. A mobile allergen test system that allows for accuracy and precision of drug testing, not only within one study site but also done at multiple centers in diverse locations, but also that will result in reproducible results across different studies conducted over different years or many countries or globally, is desirable. This may permit an ability to compare study findings directly for each drug tested, and ultimately to be able to compare directly between medications to assess relative drug risk benefit profiles important to patient treatment and drug regulation.
The present disclosure pertains to apparatuses for and methods of studying allergy and asthma in a safe and reproducible manner that may allow patient screening to recruit patients effectively who are truly symptomatic to the allergen tested, a consistent allergen exposure for all patients in the study, and a uniform and naturalistic level of control of airborne allergen exposure to control type and amount of allergen exposure applied safely.
According to an aspect of the present disclosure, a mobile chamber apparatus may include: a support structure including a plurality of inflatable support members; and a chamber assembly including a top wall, a bottom wall, and at least one side wall coupled between the top and bottom walls. In an installed state, the support structure may be coupled to the chamber assembly and may support the chamber assembly so that the top wall, the bottom wall and the at least one side wall enclose an interior space.
The apparatus may further include a plurality of connectors for detachably coupling the support structure and the chamber assembly.
At least a portion of the plurality of inflatable support members may include at least one transverse section, and the plurality of connectors may include first connectors that couple the transverse section to the top wall. The first connectors may include a plurality of cable elements, each of the cable elements fixed to and extending between an interior side of the transverse section and an exterior side of the top wall so that the top wall is at least partially suspended from the transverse section. The cable elements may be spaced apart generally along a length of the transverse section.
At least a portion of the plurality of inflatable support members may include at least one upright section, and the plurality of connectors may include second connectors that detachably couple the upright section to the at least one side wall. Each of the second connectors may include: at least one sleeve mounted to one of the upright section and an exterior side of the side wall; at least one base mounted to the other of the upright section and the exterior side of the side wall; and at least one elongate rod member that couples the base and the sleeve. The base and the sleeve may each slidingly receive the rod member. The at least one sleeve may be mounted generally along a height of the side wall, and the at least one rod member may extend generally along the height of the sidewall. The second connector may include a plurality of bases spaced apart generally along a height of the upright section, and the sleeve may include a plurality of openings, each of the plurality of openings positioned correspondingly to a respective one of the plurality of bases, the openings facilitating connection between the at least one rod member and the plurality of bases.
The apparatus may further include a plurality of spacer elements coupled between the plurality of inflatable support members. Each of the spacer elements may extend between and is fixed to an adjacent pair of the plurality of inflatable support members. Each of the spacer elements may include first and second ends that are each detachably connected to a respective upright section of the adjacent pair. At least a portion of the spacer elements may be coupled to the at least one side wall. The plurality of connectors may include third connectors that detachably couple the spacer element to the at least one side wall. The third connectors may include releasable loops that are fixed to the at least one side wall and receive the spacer element.
Each of the plurality of inflatable support members may include first and second elongate upright sections, and at least one transverse section extending between upper ends of the first and second upright sections. The at least one transverse section may include first and second elongate transverse sections, an outer end of each transverse section coupled to the upper end of a respective upright section. Inner ends of the transverse sections may be coupled together, and each of the first and second transverse sections may be inclined upwardly between the outer and inner ends. For each of the plurality of inflatable support members, the upright and transverse sections may be linked in fluid communication so that inflation of one of the sections causes inflation of each section. The support structure may further include a plurality of longitudinal sections that extend between the transverse sections. Each of the plurality of inflatable support members may be linked in fluid communication by the plurality of longitudinal sections so that inflation of one of the plurality of inflatable support members causes inflation of each of the plurality of inflatable support members.
The plurality of side walls may include a left side wall, a front side wall, a right side wall, and a back side wall. Each of the side walls may have generally equivalent width dimensions. The apparatus may further include at least one inlet disposed between an adjacent pair of the side walls for delivering a supply airflow to the interior space. The chamber assembly may further include a plurality of chamfered walls, and each of the plurality of chamfered walls may be arranged between an adjacent pair of the side walls. For each of the plurality of chamfered walls, an angle between the chamfered wall and each of the side walls of the adjacent pair may be substantially less than 90 degrees. The angle may be approximately 45 degrees. Each of the plurality of chamfered walls may have generally equivalent width dimensions, and the width dimension of the chamfered walls may be smaller than the width dimension of the side walls. The apparatus may further include at least one inlet disposed in at least one of the plurality of chamfered walls for delivering a supply airflow to the interior space. The apparatus may further include at least one outlet disposed in the top wall for delivering a return airflow from the interior space.
The chamber assembly may further include an airlock subchamber, at least one first door arranged between an exterior of the chamber assembly and the airlock subchamber, and at least one second door arranged between the airlock subchamber and the interior space.
The chamber assembly may be formed of at least one fabric material that provides a barrier to air and moisture, and provides a generally continuous seal between the top wall, the bottom wall, and the plurality of side walls. At least a portion of the chamber assembly may be formed of an electrostatically dissipative material.
The apparatus may further include at least one mechanism for introducing an allergen into the interior space.
The apparatus may be combined with an environmental control unit for delivering a supply airflow to the interior space having at least one of a controlled temperature and humidity. The environmental control unit may deliver a return airflow from the interior space.
According to an aspect of the present disclosure, a kit of parts may include: a plurality of inflatable support members, each of the plurality of inflatable support members including at least one transverse section and at least one upright section; a top wall; at least one side wall; a plurality of first connectors for coupling the transverse sections to the top wall; and a plurality of second connectors for coupling the upright sections to the at least one side wall. In an installed state, the transverse sections may support the top wall and the upright sections may support the at least one side wall so that the top wall and the at least one side wall enclose an interior space.
According to an aspect of the present disclosure, a method of installing a mobile chamber apparatus may include: at a first location, providing a support structure including a plurality of inflatable support members; at the first location, providing a chamber assembly including a top wall, a bottom wall, and at least one side wall coupled between the top and bottom walls; coupling the plurality of inflatable support members to the chamber assembly; and inflating the plurality of inflatable support members so that the support structure supports the chamber assembly and the top wall, the bottom wall and the at least one side wall enclose an interior space at the first location.
The step of inflating may be carried out subsequent to the step of coupling.
The step of coupling may include coupling transverse sections of the plurality of inflatable support members to the top wall. The step of coupling may include fixing a plurality of cable elements between the transverse sections and an exterior side of the top wall.
The step of coupling may include detachably coupling upright sections of the plurality of inflatable support members to the at least one side wall. The step of coupling may include sliding an elongate rod member to be received by a base mounted to one of the upright section and an exterior side of the at least one side wall and a sleeve mounted to the other of the upright section and the exterior side of the at least one side wall.
The method may further include connecting a plurality of spacer elements to the plurality of inflatable support members, each of the spacer elements extending between and fixed to an adjacent pair of the plurality of inflatable support members. The step of connecting may include detachably connecting each of first and second ends of the spacer element to a respective upright section of the adjacent pair. The step of connecting may include connecting at least portion of the spacer elements to the at least one side wall.
The method may further include, for each of the plurality of inflatable support members, linking upright and transverse sections in fluid communication so that, in the step of inflating, inflation of one of the sections causes inflation of each section.
The method may further include linking the plurality of inflatable support members in fluid communication by a plurality of longitudinal sections so that, in the step of inflating, inflation of one of the plurality of inflatable support members causes inflation of each of the plurality of inflatable support members.
The method may further include delivering a supply airflow to the interior space. The at least one side wall may include a plurality of side walls, and the supply airflow may be delivered to at least one inlet disposed between an adjacent pair of the plurality of side walls. The at least one side wall may include a plurality of side walls, and the supply airflow may be delivered to at least one inlet disposed in a chamfered wall arranged between an adjacent pair of the plurality of side walls. The method may further include cleaning the supply airflow and controlling at least one of temperature and humidity of the supply airflow.
The method may further include delivering a return airflow from the interior space. The return airflow may be delivered from at least one outlet disposed in the top wall.
The method may further include introducing an allergen into the interior space. The method may further include exposing at least one human patient to the allergen in the interior space. The method may further include assessing the exposure of the at least one human patient to the allergen.
The method may further include: decoupling at least a portion of the plurality of inflatable support members from the chamber assembly; deflating the plurality of inflatable support members; transporting the support structure and the chamber assembly to a second location remote from the first location; inflating the plurality of inflatable support members; and coupling the at least a portion of the plurality of inflatable support members to the chamber assembly.
According to an aspect of the present disclosure, a mobile chamber apparatus may include a support structure, and a chamber assembly. In an installed state, the support structure may support the chamber assembly so that the chamber assembly encloses an interior space. The apparatus may be combined with an environmental control unit for delivering a supply airflow to the interior space.
The combination may further include a plurality of inlets in a generally symmetrical arrangement for delivering the supply airflow to the interior space from the environmental control unit. The chamber assembly may include a plurality of side walls, and each of the side walls has generally equivalent width dimensions. The chamber assembly may further include a plurality of chamfered walls, and each of the plurality of chamfered walls may be arranged between an adjacent pair of the side walls. At least one of the plurality of inlets may be disposed in each of the plurality of chamfered walls.
The environmental control unit may deliver a return airflow from the interior space. The combination may further include a plurality of outlets in a generally symmetrical arrangement for delivering the return airflow to the environmental control unit from the interior space. The plurality of outlets may be positioned above the plurality of inlets. The chamber assembly may include a top wall, and the plurality of outlets may be disposed in the top wall.
The combination may further include at least one mechanism for introducing an allergen into the interior space.
According to an aspect of the present disclosure, a method may include: at a first location, installing a mobile chamber apparatus including a support structure supporting a chamber assembly so that the chamber assembly encloses an interior space; at the first location, coupling an environmental control unit to the apparatus to deliver a supply airflow to the interior space; introducing an allergen into the interior space; and exposing at least one human patient to the allergen in the interior space.
The supply airflow may be delivered to the interior space in a generally symmetrical manner. The method may further include, at the environmental control unit, delivering a return airflow from the interior space. The return airflow may be delivered from the interior space in a generally symmetrical manner. The return airflow may be delivered from the interior space at a position above where the supply airflow is delivered to the interior space.
The method may further include, at the environmental control unit, cleaning the supply airflow and controlling at least one of temperature and humidity of the supply airflow.
The method may further include: transporting the mobile chamber apparatus and the environmental control unit to a second location remote from the first location; at the second location, installing the mobile chamber apparatus so that the chamber assembly encloses the interior space; at the second location, coupling the environmental control unit coupled to the apparatus for delivering a supply airflow to the interior space; introducing an allergen into the interior space; and exposing at least one human patient to the allergen in the interior space.
Other aspects and features of the teachings disclosed herein will become apparent, to those ordinarily skilled in the art, upon review of the following description of the specific examples of the present disclosure.