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Keratoconus (KC) shows several distinctive features in clinical appearance, disease progression, and treatment in children compared with adults. Therefore, diagnostic, clinical care, and therapeutic approaches are different. However, pediatric keratoconus is often undiagnosed and thus untreated in many cases. Once diagnosis has been made, compliance with treatment recommendations is often poor. Pediatric keratoconus also tends to have more rapid progression than in adults; therefore, early detection and treatment are paramount to prevent serious vision impairment, which can affect the child’s development. This review of pediatric keratoconus discusses important issues such as worldwide epidemiology, clinical features in children compared to adults, and challenges in diagnosis and treatment and focuses on the most appropriate management strategies based on the best available current evidence.

e15268 Background: Typically cancer vaccines for relapse prevention in epithelial ovarian cancer (EOC) are administrated in distant anatomical sites away from the primary tumor location. Ideally for EOC relapse prevention vaccines we should explore different anatomical sites related with the original tumor location and nearby lymph nodes, in order to observe if the administration would have better clinical impact due to a potential access to the tumor microenvironment. Moreover most trials for EOC relapse prevention use one or few targets and is mainly unknown if they are relevant to promote EOC relapse. We treated EOC patients with a multi-peptide vaccine administered in lymph nodes (LN) and in the peritoneum area and were able to suppress cancer relapse with not significant adverse effects after eight years. Methods: We enrolled n = 25 EOC patients in our study and identified by systematic review and validated by siRNA six proteins involved in EOC relapse and fourteen peptides were predicted. Twelve peptides were immunogenic by Granzyme B ELISPOT, DTH and ELISA. Patients were immunized with the vaccine in axillary and inguinal LN subcutaneously every week for four weeks, every two-weeks four times and finally every month for a total of thirty-six months. Clinical and laboratory evaluations were performed every 2-months and at the end of the study. Results: 100% of the patients developed both antibodies against all the peptides by ELISA and CD8 specific cells. The peptides of the six proteins were able to induce T cell expansion in both peptides and purified protein (p = 0.0001) and (p = 0.05), respectively for Ape-1. The selected targets were all able to induce DTH and ELISA responses with statistical significance. Peptides predicted from Bcl-2, survivin, Ape-1, Sox2, EGFR and RCAS1/EBAG9 were able to increase and sustain the levels of Granzyme B ELISPOT. Bcl-2 A peptide (p = 0.001), Bcl-2 B (p = 0.005), Bcl-2 C (p.0002), survivin A (p = 0.001), Survivin C (0.05), Ape-1 A (0.0001), Ape-1 D (p = 0.001), Sox2 A (p = 0.003), Sox2 B (p = 0.0001), EGFR B (p = 0.0001) and EGFR D (p = 0.001). Conclusions: Treating EOC patients in remission in zones hardly explored previously in order to potentially improve the activation of antigen-specific Th1 and CD8 cells with specific peptides seems promising as a feasible and safe approach to prevent EOC relapse.

3138 Background: Clinical effective multi-antigen active immunotherapy for colorectal cancer (CRC) is still limited and most studies have failed. We consider this is because the targets in some of the studies are not oncogenic drivers. This is especially important for patients that progressed to standard of care treatment. Also, most of the studies with Immune checkpoint inhibitors (ICH) have failed in CRC but potentially may impact and provide better outcomes if used as combination therapies. We treated CRC patients with progressive disease in a pilot study n = 15 and found clinical responses that correlate with the CD8, delayed-type hypersensitivity (DTH) and Th1 parameters. After patients achieved remission we used the same peptides to prevent relapse with clinical and statistics significance. Methods: N = 15 CRC patients were enrolled in this pilot trial after approval for the ethic IRB committee from CICS Mexico. Patients were treated with an intradermal vaccine every week for four weeks, every two weeks four times in axillary and inguinal lymph nodes (LN) areas, and finally subcutaneously every month six times in the sites with tumor activity. Previously to the treatment we perform Granzyme B ELISPOT, ELISA, DTH and CT scan as initial controls. We delivered intradermal four peptides from sixteen peptides predicted from four proteins such as Fascin-1, Ape-1, VCP and RCAS1. Results: 86% of the patients had an objective clinical responses and 14% stable disease. All the patients had a correlation with the immunological assays as following. 58% of patients had an increased in the CD8 cells demonstrated by Granzyme B; DTH reactions were gradually increasing and by the first month of treatment the DTH were positive for Fascin-1 (78%), Ape-1 (85%), VCP (95%) and RCAS1 (83%) peptides. The more immunogenic peptides by ELISA were Fascin-1 A (P = 0.001), Fascin-1 D (P = 0.005), Ape-1 C (p = 0.001), VCP A (P = 0.003), RCAS1 A (p = 0.001) and RCAS1 B (P = 0.01). Conclusions: The treatment was effective with CR and SD responses. Once we validate this data we are planning a clinical study combining the treatment with low dose of ICH. Currently all the patients with CR are now under relapse prevention. We are still treating the patients with SD until disease progression. Importantly we believe that this data may impact the PFS and OS in CRC patients who have Karnoksky > to 80% despite progressive disease to standard of care.

Rationale: Because of increased levels of airborne particulate matter in Southwest Asia, deployed military personnel are at risk for developing acute and chronic lung diseases. Increased respiratory symptoms are reported, but limited data exist on reported lung diseases.Objectives: To evaluate new respiratory complaints in military personnel returning from Southwest Asia to determine potential etiologies for symptoms.Methods: Returning military personnel underwent a prospective standardized evaluation for deployment-related respiratory symptoms within 6 months of returning to their duty station.Measurements and Main Results: Prospective standardized evaluation included full pulmonary function testing, high-resolution chest tomography, methacholine challenge testing, and fiberoptic bronchoscopy with bronchoalveolar lavage. Other procedures including lung biopsy were performed if clinically indicated. Fifty patients completed the study procedures. A large percentage (42%) remained undiagnosed, including 12%...

e17079 Background: There are several reports of increased of SUV in the lymph nodes of cancer patients after immune manipulation such as the administration of vaccines and checkpoint inhibitors. However the clinical importance of these phenomena is poorly understood. The administration of two immunogenic drugs and eight peptides in HGSOC induced atypical bright zones in multiple lymph nodes and, in areas with microscopic disease where potentially we can have cancer stem cells (CSC’s). Methods: We enrolled N = 10 HGSOC after the local IRB ethic committee approval. All the patients had 3 recurrences with mPFS = 8 months of the third relapse. The last FDG-PET scan was used as basal image for the study. Blood was collected for cellular and humoral immunology analysis such as Granzyme B ELISPOT and ELISA. Tissue was used for IHC analysis for the evaluation of CD8, FOXP3, Th1, and proteins related with CSC’s. The patients received 50 mg of oxaliplatin and 30 mg of doxorubicin total dose every week four times simultaneously with multi peptide immunotherapy. A second FDG-PET scan was performed after the termination of the treatment. Results: After the treatment 100% of the patients showed intense atypical bright uptake areas in lymph nodes and in the peritoneum. There was a correlation between the brightness intensity (SUV), and the Granzyme B production (p = 0.001). We found multiple bright small lesions in the peritoneum that were not visible before treatment. We demonstrated the presence of proteins related with CSC’s in the original tumor tissue and an antibody immune response against EGFR (P = 0.005), Ape-1 (p = 0.003) and Bcl-2 (p = 0.05). Conclusions: Immunotherapy may produce hypermetabolic activity that could lead to overtreatment when evaluated by FDG-PET in HGSOC. Vaccination may activate lymph nodes and anti-cancer immune interventions may also activate CD8 and Th1 cells able to accumulate in CSC’s clusters and increased notably the SUV, which may lead to false relapse interpretation by the radiologists and oncologists.

Military personnel are a unique group of individuals referred to the pulmonary physician for evaluation. Despite accession standards that limit entrance into the military for individuals with various pre-existing lung diseases, the most common disorders found in the general population such as asthma and chronic obstructive pulmonary disease remain frequently diagnosed. Military personnel generally tend to be a more physically fit population who are required to exercise on a regular basis and as such may have earlier presentations of disease than their civilian counterparts. Exertional dyspnea is a common complaint; establishing a diagnosis may be challenging given the subtle nature of symptoms and lack of specificity with pulmonary function testing. The conflicts over the past 10 years in Iraq and Afghanistan have also given rise to new challenges for deployed military. Various respiratory hazards in the deployed environment include suspended geologic dusts, burn pits, vehicle exhaust emissions, industrial air pollution, and isolated exposure incidents and may give rise to both acute respiratory symptoms and chronic lung disease. In the evaluation of deployed military personnel, establishing the presence of actual pulmonary disease and the relationship of existing disease to deployment is an ongoing issue to both military and civilian physicians. This paper reviews the current evidence for chronic lung disease in the deployed military population and addresses any differences in diagnosis and management.

Military deployment to Southwest Asia since 2003 in support of Operations Enduring Freedom/Iraqi Freedom/New Dawn has presented unique challenges from a pulmonary perspective. Various airborne hazards in the deployed environment include suspended geologic dusts, burn pit smoke, vehicle exhaust emissions, industrial air pollution, and isolated exposure incidents. These exposures may give rise to both acute respiratory symptoms and in some instances development of chronic lung disease. While increased respiratory symptoms during deployment are well documented, there is limited data on whether inhalation of airborne particulate matter is causally related to an increase in either common or unique pulmonary diseases. While disease processes such as acute eosinophilic pneumonia and exacerbation of preexisting asthma have been adequately documented, there is significant controversy surrounding the potential effects of deployment exposures and development of rare pulmonary disorders such as constrictive bronchiolitis. The role of smoking and related disorders has yet to be defined. This article presents the current evidence for deployment-related respiratory symptoms and ongoing Department of Defense studies. Further, it also provides general recommendations for evaluating pulmonary health in the deployed military population.

Introduction As part of an international response to the Ebola virus disease (EVD) outbreak, the US Department of Defense has deployed thousands of personnel to help train and augment international health care workers. The transmission risk of this deadly virus to health care workers has been extreme, demonstrating the importance of safe practices while caring for these patients. Medical simulation training is well recognized as an integral component for disease outbreak preparedness. Therefore, the US Government created a program of instruction that outlines a formalized EVD training program, using high-fidelity simulation, which projects both an understanding of the disease and its transmission risks. Methods Two 5-day training courses were established to provide training to the 65-member Department of Defense Ebola Response Team, which would be activated during a stateside Ebola outbreak. This training consisted of Ebola-specific protocols, personal protective equipment familiarization, and scenario-based certification for physicians, nurses, and public health trainers. Simulation was used to replicate the work environment inside an Ebola treatment unit. Results Three comprehensive clinical scenarios covering a wide spectrum of EVD presentations were designed around details of published cases to provide the most realistic and relevant EVD training available. The authors conducted 10 iterations of the 3 EVD clinical scenarios totaling more than 1100 hours of simulation training. Conclusions Quality practical exercises to include specialized task performance and collective teamwork training relied heavily on dedicated facilities and realistic medical simulation resulting in valuable lessons learned. In future iterations, these characteristics would be imperative to a successful training course.

e15159Background: Refractory tumors are a challenge. Tumor adaptive immune infiltration in several tumors, even when refractory, is not uncommon. It is clear that the future of oncology treatments ...

e14066Background: Little is known about the immunogenicity of pediatric medulloblastomas and DIPG in order to rationally develop immunotherapies. We performed a systematic review of putative biolog...

Background Little is known why most of the cancer immunotherapies failed despite good results in pre-clinical studies. We believe that if we focus on clinically relevant multi-proteins to immune-target simultaneously in combination with drugs with potential immune properties we may improve the clinical outcomes. Methods 12 proteins overexpressed in several human tumors and associated with prognosis were identified. Indirect ELISA (IgA+ IgM + IgG) and ELISPOT was used to evaluate immunity proteins in 50 cancer patients and 50 controls. Immunohistochemistry (IHC) staining was done for proteins and CD8 T-cell quantitation. Peptides that were highly immunogenic by ELISA and ELISPOT were formulated into multi-peptide immunotherapy and with low dose of oral sorafenib. Patients treated with active progressive disease 6 months, 12 times were monitored biweekly to evaluate the immune response. Results Serum responses for all positive antigens were significantly elevated in advanced cancer patient sera when compared to donor controls (Bcl-2 p=0.001, survivin p=0.0001, EGFR P=0.005, Fascin-1 p=0.0001, Sox2 p Discussion Advanced cancer is still immunogenic and overexpressed proteins involved in clinical relevant pathways can serve as specific active immunogens. These data could be the proof of principle for the development of multi-peptide immunotherapy in combo with drugs with immune properties such as sorafenib.

Background Little information exists about the potential immunogenicity and immunotargets for DIPG. Most of the pediatric neurotumors are mainly unexplored immunologically. We studied twenty repository samples of DIPG tumors. We selected two relevant immune markers to demonstrate immune infiltration such as CD8 and Tbet and eight biologically and clinically relevant proteins found in aggressive neoplasias including DIPG. According with this preliminary data DIPG is immunogenic and six of eight relevant proteins were overexpressed. This data will open the possibility to treat this lethal tumor with active antigen-specific immunotherapy either alone and in combination. Methods N=20 repository DIPG pediatric tumors were analyzed by immunohistochemistry (IHC). Moreover we analyzed by granzyme B and IFN-gamma ELISPOT the naturally occurring immune response against predicted Th1 and CD8 epitopes from the eight proteins and we performed univariate and multivariate analysis using SAS/SAT and prism. Results six of eight bad prognosis proteins were overexpressed as following RCAS1 (80%), Fascin-1 (90%), EGFR (55%), VCP (85%), Ape-1 (95%) and Sox2 (70 %). We found 35% of expression of CD8 cells and 40% of Tbet, which is an interesting finding in terms of immune infiltration in DIPG. CD8 antigen specific by Granzyme ELISPOT against Ape-1, RCAS1 and Fascin-1 were significant as well (P=0.0001), (p=0.005) and (9=0.0001), respectively. Discussion DIPG is immunogenic according with our preliminary data and we will expand the number of samples in order to validate a large repository and move to the clinic. We predicted immunogenic peptides for each protein using repository PMBC’s and most of them were recognized by autologous PBMCS’s.

Background Some refractory cancer patients have a good Karnofsky despite refractory disease. We studied the potential immunomodulatory properties of approved drugs. We used fresh PBMC from refractory patients to study the immune effects of several drugs such as metformin, pidotimod, erdostein, esomeprazole, colchicine, bortezomib, gemcitabine, zoledronic acid and naproxen. Methods 25 high-grade serous ovarian cancer (HGSOC) and 25 colorectal cancer (CRC) subjects were included after approved protocol. The inclusion criteria include Karnofsky 80–100%, complete CT scan, acute phase proteins, granzyme B ELISPOT and antigen-specific ELISA. Results We found after 24 months of treatment in HGSOC 80% of complete response (CR), 15% of stable disease (SD) and 5 % of pseudo-progressive disease (PPD). In CRC we had 50% of CR, 30% of SD and 20% of PPD. In the patients with CR there was an immunological correlation of CD8 persistent immune response by granzyme B ELISPOT in HGSOC and CRC (p=0.0001) and PR (p=0.001), respectively. The combination was well tolerated and after 10 months of stopping the treatment some patients have persistent CD8 specific immune response by ELISPOT and ELISA. Discussion The combination of daily oral metformin, colchicine, pidotimod, erdostein, and naproxen plus weekly low dose of intravenous (IV) esomeprazole (80 mg), bortezomib (0.5 mg/m2), gemcitabine (0.5 mg/m2) and zoledronic acid (100 mg) is clinically feasible, with limited clinical toxicity. We now understand the importance of preserving the CD8 immune response and the use of immune biomarkers such as antigen specific ELISA to improve the rational and generate new combinations to improve clinical outcomes in patients with refractory HGSOC and CRC.

This is a case report of a 77-year-old female with Crohn's disease manifested by recurrent bowel obstructions, who required surgical resections on two occasions but no further medical treatment. She presented 2 years later with pulmonary infiltrates, hilar adenopathy, and multiple lung masses. Biopsies of the masses demonstrated noncaseating granulomatous inflammation and fibrosis similar to the pathology from her bowel resection. Six months later, these pulmonary lesions partially resolved without therapy. This case illustrates significant pulmonary manifestations of Crohn's disease in the absence of active gastrointestinal disease.

Background: Meloxicam and nimesulide have been studied as potential cancer immunomodulatory agents. Those drugs have been shown to have immune stimulatory effects on the tumor stroma and the microenvironment of several tumors including pancreatic ductal adenocarcinoma. They have several immune effects in vitro and in animal models. We compared the immunomodulatory activity of two preferential Cox-2 inhibitors drugs, meloxicam and nimesulide in advanced pancreatic cancer patient’s peripheral blood mononuclear cells (PBMCs) with good and poor Karnofsky. Materials and Methods: Repository PBMCs from advanced pancreatic patients with Karnofsky < 50% (n=10) and > 80% (n=10) were stimulated with different concentrations of meloxicam and nimesulide in vitro. We performed dose-response curve with concentrations of both drugs ranging from 0.5, 1, 10, 50 and 100 μM and we performed the ELISPOT assays for Interferon-gamma using human anti-CD3 and CMV whole lysate as basal T cell stimulation. Th2 cytokines were measured as well by ELISPOT and Cytokine ELISA. Results: In patients with Karnofsky > 80% both meloxicam and nimesulide were effective in promoting IFN-gamma production after stimulation with both drugs starting at 0.5 μM. The use of meloxicam was associated with significant production of IFN-gamma at 0.5 μM (p Meloxicam and nimesulide treatment resulted in different responses in PBMCs IFG-gamma production from pancreatic cancer patients that had a Karnofsky Additionally PBMCs treated with nimesulide in both groups were able to decrease Th2 cytokines such as IL-6, IL-18, TNF-alpha and IL-8 (statistical analysis in progress). Discussion: This preliminary data suggests that the use of meloxicam and nimesulide as putative immunomodulatory drugs may be less effective when pancreatic patients have a poor Karnosky although at high concentration they are effective. Also, the potent induction of IFN-gamma in patients with a good Karnofsky suggest synergy of these drugs in combination with standard of care treatment, immunogenic chemotherapy, anti-stroma strategies and active specific immunotherapy as a combinatorial approach to move forward into animal models of pancreatic cancer and eventually into the clinic. Grant Support: Junior Physician Scientist Fellowship Grant from CICS. Citation Format: Juan Marquez, Erik Ramos, Pedro Alejandro Lucero-Diaz, Fernando Durazo-Bustamante, Gerardo Palacios Diaz De Leon, Rosana Soto-Soto, Sara Carrillo-Marquez, Arturo Suplee-Rivera, Alejandro Camacho-Hernandez, Daniel Camacho-Gil.{Authors}. Meloxicam and nimesulide modulate immunity in pancreatic cancer. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr A75.

Purpose: The study objective was to determine differences in the proportion of supranormal pulmonary function tests (PFTs) between active duty military personnel and a similar non-active duty population. Given the emphasis on cardiovascular fitness in the military, it has been hypothesized that regular exercise in this cohort leads to an increased proportion of supranormal PFTs. We hypothesized a comparison of PFTs would identify no differences in the ratio of supranormal to normal PFTs between the active duty and non-active duty populations. Methods: A retrospective chart review was conducted of all pulmonary function testing studies at Brooke Army Medical Center from 2006-2011. Studies were included with either a forced vital capacity or forced expiratory volume at one second >110% predicted with both values greater than 100% predicted. A comparative analysis was performed for patients between the ages 18 to 50 based on active duty status. Further analysis was performed on all ages to determine the distribution of supranormal findings in the entire study population. Results: A total of 16,600 interpreted pulmonary function tests were queried. Of those, 4303 (31.6%) were active duty patients and 9306 (68.4%) were non-active duty patients. From all the PFTs reviewed, a total of 912 (6.7%) were identified as supranormal. When further analyzed, 381 (9.4%) of active duty age 18-50 were supranormal, 175 (12.4%) of non-active duty patients ages 18-50 were supranormal, and 356 (4.7%) of non-active duty patients age greater than 50 were supranormal. Conclusion: This study revealed no significant difference in the proportion of supranormal to normal PFTs in an active duty versus non-active duty population of the same age range. Based on these findings, no assumption should be made that supranormal PFTs are more common in military personnel. Interpretation of normal PFTs in active duty personnel undergoing evaluation should not differ from any typical patient.

e22527Background: The potential clinical important targets for synovial sarcoma (SS) are mainly unknown. We performed a systematic review and we found eight potential proteins to be targeted in thi...

e15705Background: The discovery of biological relevant targets to design effective active antigen specific immunotherapy for pancreatic ductal adenocarcinoma (PDAC) is extremely important. In terms...

e17067Background: Some antibiotics have been studied as potential cancer immunomodulatory agents. We compared the ability of two commonly used antibiotics in human peripheral blood mononuclear cell...

Our understanding of the immune responses to pancreatic tumors is very limited. Analysis of the preexisting immune responses against a panel of tumor-associated antigens could help generate new immune-based therapies and diagnostic tools. Furthermore, the majority of the few studied tumor-associated antigens found in pancreatic cancer are not clinically relevant or important for cancer cell survival. Animal and clinical immunotherapeutic studies have demonstrated that there is immune selection and immune escape against most of these antigens. Overactivation of the epidermal growth factor pathway, apoptosis-related proteins and death resistance of cancer stem cells and tumor stroma have been observed in human pancreatic cancer and often are associated to overexpression or deregulation of several proteins including EGFR, Her-2, Bcl-2, survivin, Wnt-1, and Sox2. EGFR, Her-2, Bcl-2, survivin, Wnt-1, and Sox2 are implicated in tumor aggressiveness, progression, resistance, and metastasis. Overexpression of these proteins in the tumor cells and tumor stroma of advanced pancreatic cancer, and the lack of relevant mutations make them reliable targets for clinical immunotherapy trials. We designed long peptides representing immunogenic T helper and CTL epitopes for all these six proteins. The immune response was studied in pancreatic cancer (n=15), pancreatitis (n=17) and matched controls. PBMCs were analyzed to determine Th1 and Th2 immune response by production of IFN-γ and IL-10 respectively using an ELISPOT assay. Sera and ascites fluid were used for the study of the humoral immune response by ELISA using human anti-IgG and human anti-IgA. We detected significant preexisting humoral and cellular immune responses against these peptides in patients suffering from advanced pancreatic cancer. In this study, we demonstrated that this panel of proteins could be targets for humoral and cellular immune recognition in pancreatic cancer patients whereas no detectable responses were found in healthy patients. Our results suggest that a Th2 immune response is present more often in this cohort and that it could be associated with a poor prognosis measured by overall survival. In conclusion, Th2 and ascites IgA immune responses against proteins important for tumor survival that are overexpressed in cancer cells and tumor stroma were common in our cohort of pancreatic cancer patients. Some of these proteins could serve as broad-spectrum tumor antigens to target in peptide vaccine immunotherapy trials to achieve better clinically relevant responses in pancreatic cancer patients. Citation Format: Jose V. Torres, Gardner B. Murray, Ramon Cabello, Eduardo Flores, Alejandro Camacho, Pedro A. Lucero, Anton Ostashko, Roger Dela Cruz, Jr., Fernando Durazo, Xia Li, Lizette Rodriguez, Erik Ramos, Juan Pablo Marquez-Manriquez. Preexisting immune responses against EGFR, Her-2, Bcl-2, survivin, Wnt-1, and Sox2 in pancreatic cancer patients. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Progress and Challenges; Jun 18-21, 2012; Lake Tahoe, NV. Philadelphia (PA): AACR; Cancer Res 2012;72(12 Suppl):Abstract nr A54.

When the tracheal mucosa is bypassed via endotracheal tube (ETT) intubation or from a surgically placed tracheostomy, humidification is essential to preserve tracheobronchial mucosal integrity [1]. Without humidification, the tracheal mucosa will lose ciliary function, develop inspissated secretions, and the underlying connective tissue will undergo structural changes [2–5]. Williams et al. performed a meta-analysis evaluating the relationship between the humidity and temperature of inspired gas and airway mucosal function [6]. They developed a model suggesting above or below optimal temperature, and humidity conditions can lead to impaired airway mucosal dysfunction, or, vice versa, that adequate mucociliary function is an indicator of ideal humidification. Oostdam et al. showed animals that inspired dried air demonstrated a significant reduction of extravascular water of the loose connective tissue of the airways and an increase in airways resistance to histamine [2]. ETT occlusion secondary to thickened or dried secretions is also strongly linked to suboptimal humidification [5, 7]. The most common way to avoid these and other potential complications (Box 1) is accomplished by applying humidification from non-­heated-wire humidifiers, heated-wire humidifiers, or a heat and moisture exchanger (HME) [4, 8]. The goal of each of these humidification devices is to provide tracheal humidification consisting of heat and moisture to the inspired gas with a minimum of 30 mgH2O/l or 100% relative humidity with a delivered gas at 30°C [4, 5].

Exercise-induced bronchospasm (EIB) has a prevalence of 6% to 7% in United States Army personnel and 3% to 13% in professional athletes. There are reported concerns that military personnel with EIB will have increased airway hyperreactivity or significant dyspnea while wearing the standard military M40 protective mask. The objective of this study is to determine whether the M40 protective gas mask increases airway hyperreactivity in military personnel with exertional dyspnea and the diagnosis of EIB.Ten active duty military with EIB (defined as history of exertional dyspnea, normal spirometry, and reactive methacholine challenge test) and 10 normal control subjects were evaluated. Both the participants and control subjects underwent baseline exercise challenge testing (ECT) with and without the M40 protective mask. Forced expiratory volume in one second (FEV1) (percent predicted) post ECT was compared to baseline FEV1 within and between groups along with exercise time.There was no statistical difference in between individuals and between groups wearing the M40 mask. None of the study group had a positive ECT exercising without the M40 mask while 20% of the study group with EIB had a positive ECT wearing the M40 mask.Military personnel with EIB who exercised with the M40 protective mask did not overall have significantly increased airway hyperreactivity compared to control subjects. Screening ECT may be beneficial in identifying those susceptible persons who report symptoms while wearing the M40 protective mask.