As the end organ for the treatment of local diseases or as the route of administration for systemic therapies, the lung is a very attractive target for drug delivery. It provides direct access to disease in the treatment of respiratory diseases, while providing an enormous surface area and a relatively low enzymatic, controlled environment for systemic absorption of medications. As a major port of entry, the lung has evolved to prevent the invasion of unwanted airborne particles from entering into the body. Airway geometry, humidity, mucociliary clearance and alveolar macrophages play a vital role in maintaining the sterility of the lung and consequently are barriers to the therapeutic effectiveness of inhaled medications. In addition, a drug's efficacy may be affected by where in the respiratory tract it is deposited, its delivered dose and the disease it may be trying to treat.

https://bpspubs.onlinelibrary.wiley.com/doi/epdf/10.1046/j.1365-2125.2003.01892.x

Pulmonary drug delivery. Part I: Physiological factors affecting therapeutic effectiveness of aerosolized medications

Although coronary angiography defines regions of potential ischemia in patients with coronary-artery disease, accurate assessment of the presence and functional importance of ischemia requires appraisal of regional and global left ventricular function during stress. To perform such assessment, we developed a noninvasive real-time radionuclide cineangiographic procedure permitting continuous monitoring and analysis of left ventricular function during exercise. In 11 patients with coronary disease who had normal regional and global ventricular function at rest, new regions of dysfunction developed during exercise (P less than 0.001), and in 10, global ejection fraction dropped 7 to 47 per cent. Fourteen age-matched normal subjects were studied; during exercise none had regional dysfunction, and each increased global ejection fraction (average increase, 23 +/- 3 per cent [+/-S.E.], P less than 0.001 as compared with patients with coronary disease). Radionuclide cineangiography during exercise permits accurate assessment of the presence and functional severity of ischemic heart disease.

Real-time radionuclide cineangiography in the noninvasive evaluation of global and regional left ventricular function at rest and during exercise in patients with coronary-artery disease.

Captopril (SQ 14,225), an oral angiotensin converting-enzyme inhibitor, was administered to 11 patients with severe congestive heart failure (CHF). Peak effect was observed at 1.5 hours after administration. At peak effect right atrial pressure fell from 3.4 to 0.0 mm Hg, pulmonary capillary wedge pressure (PCW) fell from 22.7 to 12.3 mm Hg, mean arterial pressure (MAP) fell from 79.5 to 62.1 mm Hg, systemic vascular resistance (SVR) fell from 1989 to 1370 dyn-sec-cm-5, pulmonary vascular resistance fell from 843 to 523 dyn-sec-cm, and cardiac index (CI) rose from 1.96 to 2.43 1/min/m2. These were all statistically significant. Control plasma renin activity (PRA) was elevated (25.9 ng/ml/hr) and correlated with resting PCW (r = 0.65). The acute hemodynamic response was related to PRA: a fall in MAP (r = 0.74), a fall in PCW (r = 0.80), a fall in SVR (r = 0.45) and a rise in CI (r = 0.45). Eight patients were placed on chronic captopril therapy. After 2 or more months, their exercise time was significantly increased, from 6.8 to 11.7 minutes. Their cardiothoracic ratios showed a significant decrease, from 0.55 to 0.52, and most patients reported symptomatic improvement. Chronic response was not predicted by acute hemodynamic response. Captopril is therefore a vasodilator with both arterial and venous effects that are at least partially caused by inhibition of the renin-angiotensin system. It may be useful for the treatment of CHF.

Acute and long-term response to an oral converting-enzyme inhibitor, captopril, in congestive heart failure.

https://mukoviscidoz.org/doc/konsensus/k_en/2009JCF_article.pdf

Inhaled medication and inhalation devices for lung disease in patients with cystic fibrosis : A European consensus

Quantitation in gated perfusion SPECT imaging: the Cedars-Sinai approach.

Pulmonary deposition of aerosols in children with cystic fibrosis.

http://jnm.snmjournals.org/content/14/11/798.full.pdf

Measurement of left ventricular ejection fraction.

https://jnm.snmjournals.org/content/13/8/649.full.pdf

A new technique for the calculation of left ventricular ejection fraction.

http://jnm.snmjournals.org/content/14/10/725.full.pdf

The measurement of regional ventilation in man: a new method of quantitation.

Twenty-five children aged 8 months to 17 years were studied to determine the usefulness of computer-assisted ventilation-perfusion(V–P) scanning in analysis of regional pulmonary function in cystic fibrosis. Ventilation and perfusion scintiphotographs were compared with the patients' radiographs. Regional fractional exchanges of air and relative regional V–P ratios were obtained. Whole-lung air exchange was significantly correlated with standard pulmonary function tests and radiograph scores. Ventilation-perfusion ratio gradients were reversed in patients with predominantly upper zone disease, and regional V–P ratios were uneven in distribution. Quantitative assessment of regional ventilation and perfusion is a useful technique for assessing severity of pulmonary disease in children with cystic fibrosis.

R.H. Secker-Walker

Papers

Pulmonary deposition of aerosols in children with cystic fibrosis.

Measurement of left ventricular ejection fraction.

A new technique for the calculation of left ventricular ejection fraction.

The measurement of regional ventilation in man: a new method of quantitation.

Quantitative assessment of regional ventilation and perfusion in children with cystic fibrosis.