Therapeutic Role of Nitric Oxide in Respiratory Disease

Thomas E. Siddons, BSc, Mohammed Asif, MA, BMBCh, FRCS, and Tim W. Higenbottam, MD, MA, BSc, FRCP, University of Sheffield, Sheffield, United Kingdom

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Inhaled NO in Pulmonary Hypertensive Disorders

Pulmonary hypertension is a hemodynamic manifestation that results from a variety of conditions, such as COPD and ARDS. Primary pulmonary hypertension (PPH) differs from the previously discussed conditions because no detectable pulmonary or cardiac disease exists to explain the condition, hence the term primary pulmonary hypertension.PPH is characterized by a pulmonary artery pressure (PAP) greater than 25 mmHg during rest and increasing to 30 mmHg or more on exertion, with a cardiac output below 5 L/min-1.[19] PPH occurs more frequently in women by a ratio of 1.7:1.[20] The prognosis for survival is poor: death usually occurs within 3 years of symptom onset. Unlike ARDS, PPH is a chronic disease; as a result, the delay between symptom onset and diagnosis can be considerable.

PPH is rare. The incidence rate is 2 per million of the population per year. It is also a difficult condition to treat effectively. The goal of therapy is to sustain lung function until transplantation. The only drug currently available for effective therapy, prostacyclin (PGI2), is an endogenous prostaglandin that is involved in regulation of basal vascular tone. In the United Kingdom, this treatment costs approximately £37,000 (US $23,300) for the first year alone.[21] Prostacyclin therapy also has serious side effects; central line infections are common and may contributeto the morbidity and mortality seen in PPH.[22]

Because of the high cost and risks associated with , PGI2 , alternative therapies and delivery methods have been sought. Originally, inhaled NO was used to evaluate the potential reactivity of the pulmonary vasculature during diagnostic right heart catheterization,[23] and recently, several centers in Europe and the United States have been actively exploring the potential of inhaled NO as a therapeutic intervention. A major goal is to deliver inhaled NO to ambulatory patients.[24] Short bursts of pulsed NO delivered at the beginning of each breath, rather than throughout inspiration, may be a way to accomplish this goal. This approach reduces the volume of NO needed to sustain a patient over a reasonable amount of time, thereby reducing the size of the cylinder and the effective dose .

Experimentally, pulsed inhaled NO has been shown to be effective for lowering pulmonary artery pressure, particularly in patients with less severe disease.[25] Because equipment is now available to deliver inhaled NO to ambulatory patients (Figure 2), the medium- to long-term effects of this therapy can now be assessed.

A patient receiving pulsatile inhaled nitric oxide via nasal cannulae.

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