Novel H1N1 influenza: the impact on respiratory disease and the larger healthcare system

Influenza is a highly contagious respiratory viral infection of humans and other animals, such as birds, marine mammals, horses and a number of other species [1]. The virus circulates within species groups during seasonal epidemics (usually in the winter), undergoing enough antigenic drift to evade host immunity and cause infection in each subsequent year. Millions of humans are infected annually during these seasonal epidemics by one of three strains: H1N1, H3N2 and influenza B. Most cases are self-limited, with sufferers experiencing a fever, sore throat, malaise, cough and shortness of breath. However, some patients develop severe disease, either from primary influenza or secondary bacterial pneumonia. These patients often have underlying risk factors, such as chronic respiratory disease (e.g., chronic obstructive pulmonary disease [COPD]), immunosuppression (e.g., transplant), institutionalization or advanced age. More than 30,000 people die from complications of influenza in the USA each year [1].

In addition to these seasonal outbreaks within species groups, influenza will also move between animal populations throughout the year. This zoonotic spread can cause isolated cases of influenza in which the virus of animal origin directly infects a human host, such as H5N1 avian influenza in humans. Disease can be severe, as seen in the H5N1 cases, or more self-limited, as seen with H7N7 avian influenza. Regardless of disease severity, close contact and infection with an animal subtype of influenza can increase the risk that a novel strain will develop and take hold within humans, either through direct genetic adaptation or by reassortment with a second influenza subtype. Subsequently, a larger outbreak can develop, potentially leading to a pandemic if host factors and viral fitness are adequate.

The novel swine origin influenza H1N1 pandemic that began in March 2009 in Mexico is a classic example of an animal origin influenza virus undergoing reassortment and spreading to humans [2]. This pandemic, the first since the 1968 Hong Kong H3N2 strain, has spread to over 100 countries and continues to cause widespread disease in the Southern Hemisphere during their seasonal influenza winter, as well as in the summer months of the Northern Hemisphere. As this subtype takes hold worldwide, we must become aware of the risk to patients with respiratory illness, the risk to healthcare workers who may present with a higher risk of nosocomial acquisition, and the need to have real-time patient care data that can influence both patient outcomes and long-term healthcare preparedness.

Origin of the 2009 H1N1

Extensive influenza surveillance in animals and humans allows us to follow the genetic evolution of many subtypes of influenza A as they drift and reassort into new clades and subtypes. Animal surveillance is strongest in birds, where wild waterfowl and domesticated poultry undergo both passive and active surveillance. Both small and large genetic changes within these animals are followed and monitored, and any change (e.g., acquisition of virulence) can readily cause alarm that triggers enhancements in biosecurity and other preventative measures (e.g., vaccination). Other mammals, such as marine mammals (seals, whales and dolphins), horses and humans, also undergo ongoing surveillance.

The detection of a novel H1N1 in March 2009 in humans in Mexico and San Diego showed a very different pattern [2]. This novel virus was largely of swine origin (it contains swine, human and avian influenza origin genes) but when compared with other H1N1 subtypes, it was very distinctly different and had no close relatives on the phylogenetic tree. Was this virus truly this different genetically? Or rather was there a gap in surveillance? Within the commercial poultry industry in developed nations, aggressive surveillance occurs, but surveillance in the swine industry is limited in North America. Swine, who are particularly susceptible to both human and avian subtypes, live in close quarters and influenza spread occurs easily and efficiently. When a swine outbreak begins and is not monitored, protective measures may not be in place, and the introduction of a second influenza virus (e.g., a human subtype) can lead to reassortment and the development of a novel strain [1]. This is the likely scenario with the H1N1 virus of 2009.

The advent of H1N1 in 2009

The H1N1 virus is a triple-reassortment virus, meaning that the virus contains swine, avian and human components. Of the eight ssRNA segments, five are of swine origin (hemmaglutinin, neuraminidase, nucleoprotein, NS and M protein), two are of avian origin (the polymerase complex polymerase acidic protein and polymerase basic protein 1) and one is of human origin (polymerase basic protein 2) from seasonal H3N2 [2]. The swine components are both of North American and Eurasian lineage, while the avian is predominantly of North American origin. This virus is distinctly different from prior swine-origin triple-reassortment viruses detected in the USA over the past 5 years.

Clinical disease has been varied but most cases consist of fever, cough and sore throat. Diarrhea and vomiting appear to be more prominent when compared with seasonal influenza, a feature that is also common with avian subtype infections. The median age of patients is only 20 years, with more than 80% of cases occurring in those under 30 years of age. Severe disease has been reported with a hospitalization rate of less than 10% and mortality being reported in less than 1% of known cases [2]. However, since this pandemic is in the early stages, many of these findings are changing rapidly, and the both the lower hospitalization and death rates may not reflect a severe disease process. In fact, most hospitalizations and deaths appear to be from a primary pneumonia with associated acute respiratory distress syndrome (ARDS) and respiratory failure, a different process to the secondary bacterial pneumonia more commonly seen with seasonal influenza [3].

Most hospitalizations and deaths appear to be seen initially in patients with prior underlying medical conditions, including congenital abnormalities, rheumatologic disorders and underlying respiratory disease. Severe disease in otherwise healthy individuals has been reported, but only in a minority of cases. Asthma, in particular, appears to be a bigger risk factor for severe disease, along with obstructive lung disease. In the most serious cases, severe ARDS predominates, with poor pulmonary compliance and severe hypoxemia. Regardless of the underlying respiratory condition, the progression of the H1N1 pandemic will lead to an increase number of patients with respiratory illness, either with severe asthma exacerbations or profound respiratory failure and ARDS.

Respiratory disease & H1N1

Asthma may be a major risk factor for more severe disease. Since this is a novel subtype of influenza, we cannot rely on our humoral immune response to rapidly neutralize the virus. Instead, we must rely on our innate immunity. The 1918 H1N1 virus stimulated a very robust T-cell-driven response that lead to increased cytokine production and subsequent acute lung injury, driving the higher rates of respiratory failure death seen with the virus. The 2009 H1N1 appears to have some epitopes conserved from the seasonal H1N1 virus and thus we have a more limited and appropriate cytokine response in a primed T-cell immune system, leading to viral clearance and humoral immunity in most cases. However, in patients with asthma, those conserved epitopes can lead to increased IL-4, IL-13 and IgE production, leading to asthma exacerbations. Indeed, early reports of asthmatics infected with the 2009 H1N1 show increased wheezing, coughing and signs of an exacerbation. This has been seen in patients with both intermittent asthma and moderate-to-severe persistent disease. In addition, young children infected with H1N1 present with a component of bronchiolitis, much like respiratory syncytial virus [2]. Thus, asthma-related complications may be a prominent feature of the H1N1 pandemic in 2009 as it progresses worldwide.

In addition to asthma, the second respiratory feature of H1N1 is severe primary pneumonia. This process occurs through a primary pneumonia with severe cytokinemia, leading to acute lung injury and respiratory failure. The severe primary pneumonia appears to be more common in younger patients. The lack of severe disease in the older population has lead to speculation of protection from older H1N1 strains. Most of the features of primary pneumonia with H1N1 are poorly known, but injury appears to be severe, with high mechanical ventilator needs, including high levels of positive end expiratory pressure (PEEP) and fraction of expired oxygen. In most cases, lung protective strategies with low tidal volume ventilation have been employed, but alternative rescue therapies (e.g., high-frequency oscillatory ventilation) are largely unknown.

With the increase in severe disease with both asthma and primary pneumonia, aggressive respiratory care must be performed early and immediately. However, as the pandemic progresses, the clinical data and information on respiratory outcomes of these patients must be monitored closely in order to effect clinical practitioners in real time.

Data collection & H1N1

As the H1N1 pandemic progresses, high-risk individuals with chronic respiratory disease such as asthma and COPD are more likely to develop severe complicated disease. However, within this group of patients, many questions still remain. Is there a particular group that is most at risk? Are asthmatics on higher doses of inhaled steroids more or less likely to have severe disease? Are patients with well-controlled asthma similar to those with poorly controlled asthma? Do some patients present predominately with cough and wheezing rather than fever, thus prompting us to evaluate these patients for influenza (which may be the case)? In order to approach these questions, respiratory care practitioners must have the ability to rapidly collect and submit these data, with subsequent presentation in return to be accessible to respiratory care practitioners in the field [4].

Similarly, the rapidly changing presentation and clinical course of severe H1N1 pneumonia must be reported, analyzed and presented in a nearly real-time manner. Which patients are at highest risk for developing severe disease? (For example, it appears that morbid obesity may play a role). What are the average ventilator settings (e.g., PEEP) for these patients? Are there special mechanical ventilatory needs with these patients outside of low tidal volume lung protective strategies? Is any practitioner using noninvasive mechanical ventilation? Can the ventilators found in many governmental stockpiles provide sufficient care?

This information can help shape bedside care immediately in these patients in whom clinical course can change within minutes. During the SARS outbreak in Toronto, Canada, in 2005, the critical care community developed a method of daily communication, relaying this information and impacting care immediately. Currently, public-health reporting does not contain detailed information regarding the respiratory involvement of H1N1. Therefore, these data need to be collected from other groups (e.g., professional societies such as the Society of Critical Care Medicine or clinical trials group like ARDSnet) and be made available to all respiratory care practitioners.

Respiratory care workers & H1N1

With the rapid data collection on H1N1 respiratory disease, respiratory care practitioners must determine their risk of nosocomial acquisition of H1N1. With respiratory infectious diseases, respiratory care workers are often at the highest risk within the healthcare worker community due to their involvement with certain procedures such as bronchoscopy, nebulization of medication, intubation and mechanical ventilation [1]. During the SARS outbreak, efficient transmission of the virus to healthcare workers occurred with respiratory procedures such as intubation, noninvasive mechanical ventilation and cardiopulmonary resuscitation [1]. Although no data regarding the enhanced transmission of H1N1 during these procedures exist, the potential of respiratory care workers coming into contact with H1N1 remains high and thus respiratory care protection must be taken.

Currently, H1N1 appears to be spread mainly by larger droplets and thus a standard surgical mask will provide adequate coverage for routine contact. However, many institutions are recommending their healthcare workers wear more advanced protective equipment, such as an N-95 mask of a powered air-purifying respirator, when they are performing respiratory procedures such as bronchoscopy and medication nebulization. In addition, patient placement in negative-pressure isolation rooms may be indicated initially during these procedures, thus requiring a longer cleaning and turn-around time for procedure suites. Finally, the use of high-efficiency particulate air filters on ventilatory circuits expiratory limbs are being used in addition to the above protective methods, but limited data exist for their benefit in influenza. Thus, the coordination of clinical care and real-time data collection must be tailored to subsequent worker protection, providing the foundation for healthcare system preparedness.

Healthcare system preparedness & H1N1

As the H1N1 pandemic progresses in the Southern Hemisphere influenza season, the Northern Hemisphere continues to see sporadic cases. As we move out of the influenza season in the south to the influenza season in the north, we are likely to see a large surge in H1N1-related respiratory disease. Are we prepared for such a second wave in the fall of 2009?

Given the possibility of increases in both asthma-related complications and severe primary pneumonia, we will need a detailed regional response for respiratory and critical care. First, we must centralize our critical care to regional acute care hospitals as these patients require extensive support (e.g., oxygen needs and mechanical ventilation) that exceed the capabilities of an alternate care site [4]. Thus, the complex movement of patients to these regional centers in order to handle the regional surge is of extreme importance. Second, we need to have adequate supplies for respiratory care. Mechanical ventilators, associated respiratory equipment (e.g., tubing), high-flow oxygen and medication (albuterol) are often in short supply [5]. In resource-rich communities, these items may provide care for the immediate few, but over the prolonged pandemic, these resources may run short. In resource-poor communities, the immediate needs may not be met. Thus, a centralized process of resource allocation and management is required. Adequate allocation may in fact require the triage and distribution of certain resources when limited, providing an additional need and standard method of triage in order to ensure ethical and equal delivery of healthcare across a region.

In addition to this planned need for respiratory equipment and resources, additional unpredicted needs will arise. For example, if asthma is a feature of H1N1, our need for albuterol administration will be high. But if nebulization increases the risk of disease transmission, we will need to use metered-dose inhalers with spacers. Thus, do we have adequate supplies? Does the emergency medical services system have the ability to make the transition from nebulized to metered-dose inhaler delivery of albuterol? If we require the reuse of spacers between patients, does our infection control plan consider the adequate cleaning of these items? If we do require the use of nebulization of medication, do we have the ability to provide advanced protection for our staff and can we cohort these patients appropriately? As care for the H1N1 patient develops, our healthcare system needs to be able to respond appropriately to both larger, regional needs of surge capacity along with the rapidly changing requirements of respiratory equipment and care planning.

Conclusion

As the H1N1 pandemic advances, many questions still remain regarding high-risk respiratory illness and the care of patients with severe primary pneumonia. Chronic respiratory illness and obesity appear to be risk factors and thus we may need both increased specialized care of these patients and advanced respiratory care protection for healthcare workers. This specialized care and protection will, in turn, require a more complex regional care network in order to meet the surge of patients with H1N1 that will present as the pandemic progresses throughout 2009 and into 2010.

Financial & competing interests disclosure

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.