Noradrenaline: friend or foe?

Septic shock, systemic inflammation and pharmacological vasodilatation are often complicated by systemic hypotension despite aggressive fluid resuscitation and an increased cardiac output. If the physician wishes to restore arterial pressure to higher levels (> 80-85 mmHg), with the aim of sustaining cerebral and coronary perfusion pressure, the administration of systemic vasopressor agents, such as norepinephrine (noradrenaline), becomes necessary. However, because norepinephrine (NE) induces vasoconstriction in many vascular beds (visibly in the skin), it may decrease renal and visceral blood flow, impairing visceral organ function. This unproven fear deters clinicians from using NE more consistently. Vasodilated states, however, are often associated with impaired peripheral vascular responsiveness. In such states, unlike under normal circulatory conditions, NE may actually improve visceral organ blood flow by selectively increasing organ perfusion pressure. Data available from animal studies show that the increased organ perfusion pressures achieved with NE results in improved GFR and renal blood flow. In fact, recent sophisticated physiological analysis of its effects on the kidney shows that, even after controlling for the pressure effect, NE therapy is associated with an increase in renal blood flow after endotoxin administration. In particular, the renal Pzf (pressure at which there is no further blood flow) is decreased such that, at a constant pressure, renal blood flow increases after NE. There are no controlled human data to define the effects of NE on the kidney in the clinical context. However, many patient series have now been reported. They show a seemingly positive effect of NE administration on GFR and urine output. Our clinical experience in septic patients and cardiac patients with inflammatory or pharmacological vasodilatation is also positive. We have demonstrated a positive effect on coronary blood flow. There is no reason to fear the effect of NE. If it is used to support a vasodilated circulation after adequate intravascular filling has occurred and after a normal or increased cardiac output has been established, it is likely to be a friend not a foe.     

Renin: friend or foe?

Renin maintains blood pressure through vasoconstriction when there is inadequate salt to maintain volume. In populations where blood pressure is more often high than low, and vascular death more common than haemorrhage or dehydration, therapeutic reductions in renin secretion or response are valuable. Whether long-term benefits are due entirely to blood pressure reduction remains unproved. The pathway can be blocked at its rate-limiting step (beta blockade or direct renin inhibition), the synthesis of the active product, angiotensin II, or at the receptor for angiotensin. Because renin and sodium are the two main factors in blood pressure control, and renin levels vary inversely with sodium load, blood pressure control requires a combination of natriuresis and blocking the consequential increase in renin activity. Being a large and stable molecule, renin is among the easiest and cheapest of hormone measurements. Understanding the simple biochemistry and physiology of renin permits optimal use of the drugs acting to raise or suppress this hormone.     

Endotoxin: friend or foe?

Endotoxin in our living environment has been of increasing interest to our global community of allergists. Initially and largely studied for its capacity to mediate septic shock (and earning its "-toxin" suffix), we have since come to understand that endotoxin in the dust of many occupational settings also is an occult respiratory culprit, inducing airflow obstruction and aggravating asthma and allergies. More recently, environmental endotoxin has been implicated as a microbial exposure in early childhood that may have an atopy-protective effect by augmenting early Th1-type immune development. Although seemingly paradoxical, endotoxin's dual nature ultimately may serve to enlighten our understanding of how such bioactive exposures can interact with and guide our immune systems in both health and disease.     

Food industry: friend or foe?

Open discourse and tolerance between the food industry and public sector is limited. As a result, the public and private sectors are reluctant to collaborate on pressing nutritional issues. Those in the public sector have never heard what they could do to encourage a food company's transition towards healthier foods and beverages, whereas many in the private sector dismissed policies and actions initiated within the public sector. During my career, I have sought to engage the broadest possible stakeholder groups required to develop evidence‐based policies and with the aim of improving public health. My recent experience in industry confirmed my view about the need for scientific exchange regardless of the disagreements about policy. Open discourse and partnering is essential if we are to tackle complex food and health issues and improve the global food system. Private–public engagement can provide faster and more sustainable results than government alone without impacting profits. Moreover, a high‐quality product in smaller portions will have higher profit margins than a bargain‐sized product of lower quality. The food industry and private sector must come together to implement innovative strategies to address urgent nutritional needs.     

Beta2-agonists: friend or foe?

This review summarizes the effects of beta2-agonists on asthma severity. There has been a controversy as to whether the regularly scheduled use of beta2-adrenergic agonists increases the risk of adverse outcomes in asthma. A number of epidemiological and clinical studies have found an association between the regularly scheduled use of beta-agonist drugs and increased risk of asthma morbidity and mortality. However, this observation has not been consistent across studies. We discuss here the potential mechanisms to explain the relationship between the use of beta-agonists on a regularly scheduled basis and adverse outcomes of asthma therapy; and we provide a brief review of the effect of genetic diversity at the beta2-adrenergic receptor locus on asthma severity. Overall, the evidence suggests that the beta2-agonists in current use in the United States are generally safe and effective; friends, not foes.     

Asthma disease management: friend or foe?

The evolution of health care in the United States has recently given rise to a movement commonly referred to as "Disease Management" in which improved outcomes are sought by using a data-driven process to direct appropriate resources to patients most likely to benefit from them. Related to asthma, debate has tended to focus on studies that have demonstrated better patient-centered outcomes for patients managed by asthma specialists, rather than the ability of the goals of asthma DM to serve the interests of patients, health care providers, and health plans. This article reviews the major forces that propel the disease management movement, describes the nature of DM programs, and presents a proposal that underscores the viability of specialty care in asthma disease management. Also presented are several examples from the author's experience in Texas of practical ways that asthma specialists can become constructively engaged in the evolution of effective and efficient systems of care for patients with asthma.