Dysfunctional Immune Activation and Chronic Inflammation Might Increase Lung Cancer Risk in HIV Infection

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Highlights
  • HIV infection is independently associated with an increased risk of lung cancer.
  • With the advent of anti-retroviral therapy (ART), and improved survival rates, there has been an increase in the proportion of deaths occurring due to non-AIDS defining solid tumors, especially lung cancer.
  • Very little data currently available to predict relationship between longitudinal measurements of immune function and lung cancer risk in the setting of HIV infection.
  • This longitudinal cohort study assessed the risk of lung cancer development in HIV patients in relation to their immune function and presence of chronic lung inflammation.
Presence of impaired immune response and chronic inflammation in the background of HIV infection might contribute to an increased risk of lung cancer according to a recent longitudinal cohort study conducted in the US.
Dysfunctional Immune Activation and Chronic Inflammation Might Increase Lung Cancer Risk in HIV Infection

Aim of the Study

The researchers wished to assess whether presence of impaired or dysfunctional immunity and chronic lung infection and inflammation could contribute to an increased risk of development of lung cancer in the background of HIV infection. Currently not many studies have been conducted in this regard.

Details of the Study

Participants for the study were chosen from the amongst the Veterans Aging Cohort Study.

They should have had HIV infection for a minimum of three years. This longitudinal cohort study spanned from 1998 to 2012. The Cancer Registry was used to identify incidental cases of lung cancer.

Persons with HIV infection less than three years, and also those with a prevalent diagnosis of lung cancer and incomplete clinical and lab data were excluded.

Cox regression models were employed to assess the relationship between (CD4 cell count, CD8 cell count, CD4/CD8 ratio, HIV RNA, and bacterial pneumonia) and risk of lung cancer.

Other model adjustments were made for smoking, age, race or ethnicity, hepatitis C infection, history of chronic obstructive pulmonary disease and occupational lung disease, and alcohol and drug use.

Findings of the Study

The results of the study revealed the following -
  • 277 incidental lung cancer cases were identified from amongst 21666 participants.
  • An increased incidence of lung cancer was associated with a decreased CD4 cell count (p trend=0·001), low CD4/CD8 ratio (p trend=0·0001), more HIV RNA concentration (p=0·004), and higher number of cumulative bacterial pneumonia episodes (12 month lag only; p trend=0·0004), in distinct models for each time-updated 12 month lagged, 24 month simple moving average cumulative exposure,
  • CD4/CD8 ratio and cumulative bacterial pneumonia episodes were found to be statistically significant (p trends 0·003 and 0·004, respectively), when including these parameters in a mutually adjusted model.
Conclusions and Takeaway from the Study

The study found evidence that dysfunctional immune system activation and chronic inflammation could cause an increased incidence of lung cancer in the background of HIV infection.

The findings of the study may be employed to target lung-cancer preventive  measures among high-risk groups.

How HIV Infection May Increase Lung Cancer Risk

Smoking remains a major risk factor among HIV infected individuals for the development of lung cancer, since most of them are heavy smokers and intravenous (IV) drug users.

However, studies conducted have found that HIV infection independently showed a statistically significant risk for the development of lung cancer after adjustments for individual smoking exposure were made. The following are postulated as the possible mechanisms that operate in persons with HIV infection to increase lung cancer risk.
  • Oncogenic potential of the HIV infection itself
  • Immunosuppression and decreased immunosurveillance related to HIV infection, akin to other AIDS defining cancers
  • Recurrent lung infections and asthma lead to a chronic inflammatory state, and predisposing to lung cancer
  • HIV infection mediated genomic instability, leading to an increased susceptibility to tobacco carcinogens.
However evidence to support these potential mechanisms remains scarce.

Chronic (Dysfunctional) Immune Activation in HIV Infection

Chronic immune system activation has been known to occur in HIV infection. Such unregulated activation leads to a state of immunosuppression by decreasing CD4 cell counts, direct inhibition of B cells and damage and destruction of the architecture of tissues essential for T cell function and homeostasis such as lymph node, thymus and bone marrow. Additionally, such uncontrolled activation of the immune system causes its premature aging and senescence.

Persistent immune activation has been shown to be associated with elevated levels of inflammatory and coagulopathy markers such as hs-C-reactive protein, IL-6 and D-dimer.

The immunosuppression and chronic inflammatory state induced by chronic immune activation might probably play a role in enhancing the risk of development of lung cancer.

Scope of Future Research in This Area

It is necessary for further studies to be conducted to better understand the mechanisms such as immune dysfunction and their role in the development of lung cancer in HIV infected persons.  This might lead to development of novel treatment modalities and tools to minimize lung cancer risk in this population.

Future research employing biological markers for pulmonary infections and inflammation, is necessary to understand how lung infection and inflammation operate in HIV infected persons to increase lung cancer risk.

References:
  1. HIV Infection Is Associated with an Increased Risk for Lung Cancer, Independent of Smoking - (http://cid.oxfordjournals.org/content/45/1/103.ful)
  2. Epidemic of Lung Cancer in Patients With HIV Infection - (https:www.ncbi.nlm.nih.gov/pmc/articles/PMC3619638)
  3. Pulmonary infections and risk of lung cancer among persons with AIDS - (https:www.ncbi.nlm.nih.gov/pmc/articles/PMC2955766)
  4. Factsheet Lung cancer - (http://www.aidsmap.com/Lung-cancer/page/1044696)
  5. Biomarkers of immune dysfunction in HIV - (https:www.ncbi.nlm.nih.gov/pmc/articles/PMC3032605/)
  6. HIV-associated chronic immune activation - (https:www.ncbi.nlm.nih.gov/pmc/articles/PMC3729961/)
Source: Medindia

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