Deposition and clearance of inhaled 18FDG powder in patients with chronic obstructive pulmonary disease

Abstract

As freon is limited in its use as a generator for aerosol inhalation, powder particles are used as an alternative for inhalation therapy. The pulmonary deposition and clearance of inhaled powder particles was studied by positron emission tomography (PET) in ten patients with chronic obstructive pulmonary disease (COPD) and in five normal controls. The powder, 5 microm in mean diameter, was water soluble and labelled with 2-deoxy-2-[18F]-fluoro-D-glucose (18FDG). Powder inhalation was done with single deep inspiration from residual volume to total lung capacity. The initial deposition ratio in the right or left lung field to total inhaled dose, measured by an anteroposterior rectilinear scan, did not differ between normals and COPD patients. Ratios of radioactivity detected within the central and peripheral regions (the central to peripheral ratio) measured by the PET scan was not significantly different between COPD patients (4.8+/-2.6, mean+/-SD) and normals (2.6+/-0.8, mean+/-SD). However, the regional powder deposition in peripheral lung fields measured by the PET scan was significantly more uneven in COPD patients than in normal patients. The clearance rate of 18FDG, defined as the retention ratio of 18FDG activity to the initially deposited 18FDG at 60 and 120 min after inhalation, in the trachea, large bronchi or peripheral lung fields measured by tomographic scan showed a wider variation in COPD patients than in normals. To conclude, inhaled powder tended to be deposited more centrally and was distributed more unevenly in the peripheral lung in chronic obstructive pulmonary disease patients than in normals. This could be a limitation of powder inhalation used for therapy in chronic obstructive pulmonary disease patients.

COPD and cancer mortality: the influence of statins

“…Collectively, these data suggest that, in addition to cigarette smoking, other potential explanations should be considered. These include (1) shared genetic susceptibility;26 27 (2) delayed clearance of inhaled carcinogens because of airflow limitation;28 and (3) chronic low-grade lung and systemic inflammation associated with COPD 29. We have found previously that, in patients with COPD, systemic levels of C-reactive protein, a biomarker of systemic inflammation, is associated with a future risk of cancer mortality including those related to extrapulmonary cancers 30.…”

Genetic Predisposition to Chronic Obstructive Pulmonary Disease and/or Lung Cancer: Important Considerations When Evaluating Risk

“…Cigarette smoke contains a number of known carcinogens and a very high concentration of oxidants (18) that in combination induce inflammation leading to DNA damage and mutations in lung and airway tissues. With airflow impairment, patients are not able to fully clear the tobacco carcinogens, thus increasing the opportunity to induce DNA damage and mutations (19). In addition, the chronic and persistent oxidative stress and local inflammation have also been implicated in the pathogenesis of lung cancer (20).…”

The bioavailability and airway clearance of the steroid component of budesonide/formoterol and salmeterol/fluticasone after inhaled administration in patients with COPD and healthy subjects: a randomized controlled trial

“…Fluticasone, being more lipophilic and thus less water soluble, is more likely to be retained in the lumen of the airways and therefore, has a greater chance of being removed from the airways by mucociliary clearance and cough [11]. These differences in lipophilicity may be particularly relevant in patients with severe COPD because marked airflow obstruction will lead to greater proximal deposition of inhaled drugs [12] and therefore mucociliary clearance. Indeed, previous studies in patients with asthma and airflow obstruction have shown that the systemic exposure of fluticasone is more affected by lung function than budesonide [13,14].…”