SERIES: PULMONARY VASCULAR DISEASE
Secondary pulmonary hypertension

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Summary

Recent research has greatly improved our understanding of the pathophysiology of pulmonary hypertension. There is increasing recognition that pulmonary hypertension is an important complication of many childhood respiratory diseases including cystic fibrosis, interstitial lung diseases, upper airways obstruction and disorders of the respiratory muscles and chest wall. Chronic hypoxaemia and, in some cases, destruction of the vascular bed are the key factors. The clinical features of pulmonary hypertension are often overshadowed by those of the primary respiratory disease but newer imaging techniques allow earlier detection of this complication. This may be important in the future if new specific therapies for primary pulmonary hypertension are shown to be beneficial in secondary pulmonary hypertension.

With some conditions, such as airways obstruction due to adenotonsillar hypertrophy, treating the underlying cause leads to rapid resolution of the hypertension. However, with most disorders, such as cystic fibrosis, management is focused on treating the lung disease intensively and correcting the chronic hypoxaemia with oxygen therapy, sometimes augmented by nasal mask ventilation. However, although several new selective therapies are effective in idiopathic pulmonary arterial hypertension, their role in secondary pulmonary hypertension remains unclear.

Section snippets

INTRODUCTION

In recent years, there has been an explosion of interest in the growth, physiology and pathophysiology of the pulmonary circulation in children.1, 2, 3, 4 We now have a much greater understanding of the molecular and cellular factors that determine the structure and function of the pulmonary vasculature. Recent advances in imaging and other technologies have allowed the earlier detection and assessment of pulmonary hypertension. This improved understanding has led to the development of new

DEFINITION AND CLASSIFICATION OF PULMONARY HYPERTENSION

The same definition of pulmonary hypertension applies to both children and adults.2 Pulmonary hypertension is defined as a mean pulmonary artery pressure of ≥25 mmHg at rest or ≥30 mmHg during exercise, with a normal pulmonary artery wedge pressure (≤15 mmHg) and an increased pulmonary vascular resistance index of ≥3 Wood units × m2. The inclusion of abnormalities of exercise haemodynamics in the definition is important as some children with significant hypertension have a normal-high pulmonary

SECONDARY PULMONARY HYPERTENSION: PATHOGENESIS AND PATHOPHYSIOLOGY

The pathogenesis of pulmonary hypertension is complex and multifactorial. Three major pathological mechanisms are involved:5

  • pulmonary vasoconstriction secondary to hypoxaemia;

  • proliferation and structural remodelling of the pulmonary vasculature; and

  • progressive obstruction and obliteration of the pulmonary vascular tree.

Additionally, in children, developmental hypoplasia of the pulmonary circulation, for example due to chronic lung disease of prematurity, may be an important factor. There are

DISORDERS OF THE RESPIRATORY SYSTEM OR HYPOXAEMIA THAT LEAD TO SECONDARY PULMONARY HYPERTENSION

The most important factor in the development of secondary pulmonary hypertension is chronic alveolar hypoxia. This leads to pulmonary vasoconstriction and endothelial dysfunction. Hypoxia may be due to alveolar hypoventilation, for example, when there is airways obstruction severe enough to cause respiratory muscle failure, or abnormal central ventilatory drive; and/or ventilation/perfusion (V/Q) mismatch. The most common respiratory causes of pulmonary hypertension in children are severe

ASSESSMENT AND INVESTIGATION

Once secondary pulmonary arterial hypertension is suspected, its diagnosis, evaluation and management require a methodical approach. Pulmonary hypertension is not a simple clinical entity but is a haemodynamic abnormality common to many disorders. A careful history is important but the symptoms are often impossible to distinguish from progression of the underlying respiratory disorder. Symptoms such as dyspnoea, fatigue, lethargy, exercise intolerance, syncope, cyanosis, chest pain, palpitation

MANAGEMENT

The key principle in managing pulmonary hypertension in patients with chronic respiratory disorders is to treat the hypoxaemia by optimising lung function and gas exchange. This can be achieved by:

  • diagnosing and, if possible, removing the underlying cause (e.g. by relieving upper airway obstruction in children with adenotonsillar hypertrophy);

  • where it is not possible to correct the cause, by treating the underlying lung disease more intensively (e.g. more intensive treatment of lung infection

PRACTICE POINTS

  • Recognising and treating chronic hypoxaemia is vital in preventing the development of secondary pulmonary hypertension in chronic respiratory disease.

  • Pulmonary hypertension should be considered early in children with severe CF, myopathy, severe spinal or chest wall deformity, ILD or features of sleep-disordered breathing.

  • Overnight oxygen saturation monitoring is particularly useful in identifying occult hypoxaemia.

  • Significant hypoxaemia and pulmonary hypertension can occur in occult ILD with a

RESEARCH DIRECTIONS

  • The role of specific vasodilator therapies in children with secondary pulmonary hypertension.

  • The role of new echocardiographic techniques to assess right ventricular dysfunction and pulmonary hypertension in children (as opposed to adults) with CF, ILD and other disorders.

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