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The primary function of the bronchial epithelium is to act as a defensive barrier aiding the maintenance of normal airway function.

Bronchial epithelial cells (BEC) form the interface between the external environment and the internal milieu, making it a major target of inhaled insults. However, BEC can also serve as effectors to initiate and orchestrate immune and inflammatory responses by releasing chemokines and cytokines, which recruit and activate inflammatory cells. They also produce excess reactive oxygen species as a result of an oxidant/antioxidant imbalance that contributes to chronic pulmonary inflammation and lung tissue damage.

Accumulated mucus from hyperplastic BEC obstructs the lumen of small airways, whereas impaired cell repair, squamous metaplasia and increased extracellular matrix deposition underlying the epithelium is associated with airway remodelling particularly fibrosis and thickening of the airway wall. These alterations in small airway structure lead to airflow limitation, which is critical in the clinical diagnosis of chronic obstructive pulmonary disease (COPD).

In this review, we discuss the abnormal function of BEC within a disturbed immune homeostatic environment consisting of ongoing inflammation, oxidative stress and small airway obstruction. We provide an overview of recent insights into the function of the bronchial epithelium in the pathogenesis of COPD and how this may provide novel therapeutic approaches for a number of chronic lung diseases.

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On April 9, 2014, Aeras and the National Institute of Allergy and Infectious Diseases convened a workshop entitled "Developing Aerosol Vaccines for Mycobacterium tuberculosis" in Bethesda, MD.

The purpose of the meeting was to explore the potential for developing aerosol vaccines capable of preventing infection with M. tuberculosis (Mtb), preventing the development of active tuberculosis (TB) among those latently infected with Mtb, or as immunotherapy for persons with active TB.

The workshop was organized around four key questions relevant to developing and assessing aerosol TB vaccines:

• What is the current knowledge about lung immune responses and early pathogenesis resulting after Mtb infection and what are the implications for aerosol TB vaccine strategies?
• What are the technical issues surrounding aerosol vaccine delivery?
• What is the current experience in aerosol TB vaccine development?
• and What are the regulatory implications of developing aerosol vaccines, including those for TB? Lessons learned from the WHO effort to develop an aerosol measles vaccine served as a case example for overall discussions at the meeting.

Workshop participants agreed that aerosol delivery represents a potentially important strategy in advancing TB vaccine development efforts. As no major regulatory, manufacturing or clinical impediments were identified, members of the workshop emphasized the need for greater support to further explore the potential for this delivery methodology, either alone or as an adjunct to traditional parenteral methods of vaccine administration.

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Over a hundred years after the first description of this disease, lung cancer represents one of the major challenges in oncology. Radical treatment cannot be introduced in more than 70% of cases and overall survival rate does not exceed 15%.

The immunosurveillance of lung cancer may be effective in early oncogenesis but is inhibited in the course of developing a clinically detectable tumor. Very low and heterogonous antigenicity of lung cancer cells leads to passive escape from anti-cancer immune defense. The cytotoxic lymphocytes (CTLs) that play a main role in the anticancer response are actively suppressed in the tumor environment and following regulatory mechanisms inhibit the recognition of tumor antigens by antigen presenting cells. The population of regulatory T cells (Tregs) is augmented and the expression of transcription factor-Foxp3 is markedly increased on tumor cells and tumor infiltrating lymphocytes (TIL). It is accomplished by M2 macrophage polarization, the activity of myeloid derived suppressor cells (MDSCs) and a significantly elevated concentration of cytokines: transforming growth factor beta (TGFβ) and IL-10 in the tumor microenvironment. Very active suppression of immune protection is the predominant role of the programmed death 1 (PD-1)-PD-L1 pathway. The blockage of this pathway was found to be an effective treatment approach; therefore the monoclonal antibodies are being intensively investigated in lung cancer patients. Cytotoxic T lymphocyte antigen-4 (CTLA-4) is the molecule capable of inhibiting the activation signal. The antibody anti-CTLA-4 improves CTLs function in solid tumors and lung cancer patients may benefit from use of this agent.

The second way in lung cancer immunotherapy is production of anti-cancer vaccines using recognized cancer antigens: MAGE-A3, membrane associated glycoprotein (MUC-1), and EGF. It was recently shown in ongoing clinical trials that combined therapies: immune- and chemotherapy, radiotherapy or targeted therapy seem to be effective.

Immunotherapy in lung cancer has an individual character-there is a need to assess the patient's immune status prior to implementation of immunomodulating therapy.

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Work-related asthma is common and yet remains a challenge to diagnose. Access to a listing of agents associated with work-related asthma has been suggested as useful in assisting in the diagnosis.

METHODS: The Association of Occupational and Environmental Clinics (AOEC) developed criteria that were used to review the peer-reviewed medical literature published in English. Based on this review, substances were designated either as a sensitizing agent or an irritant. The reviews were conducted by a board certified internist/pulmonologist/occupational medicine specialist from 2002 to 2007 and a board certified internist/occupational medicine physician from 2008- date. All reviews were then reviewed by the nine member AOEC board of directors.

RESULTS: The original list of agents associated with new onset work-related asthma was derived from the tables of a text book on work-related asthma. After 13 years of review, there are 327 substances designated as asthma agents on the AOEC list; 173 (52.9%) coded as sensitizers, 35 (10.7%) as generally recognized as an asthma causing agent, four (1.2%) as irritants, two (0.6%) as both a sensitizer and an irritant and 113(34.6%) agents that still need to be reviewed.

CONCLUSIONS: The AOEC has developed a readily available web based listing of agents associated with new onset work-related asthma in adults. The listing is based on peer-reviewed criteria. The listing is updated twice a year. Regular review of the peer-reviewed medical literature is conducted to determine whether new substances should be added to the list. Clinicians should find the list useful when considering the diagnosis of work-related asthma.

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