Dispersing the Mists: An Experimental History of Medicine Study into the Quality of Volatile Inhalations.

BACKGROUND: Dr. Nelson's Improved Inhaler was first marketed with an advertisement in The Lancet in 1865. Revolutionary at the time for its ease of use and patient-friendliness, the inhaler is still in use for self-treatment by many all over the world. On the occasion of its 150th anniversary, this study reports an experimental historical medicine approach to identify evidence for the quality of vapor inhalers. METHODS: Through accessing reviews of the device's use by the contemporary medical establishment, it was established that Dr. Nelson's Inhaler enjoyed a reputation of quality and efficacy among reputable physicians generating empirical evidence of clinical performance. There was a general absence of product performance tests during this period. Therefore, modern inhalation performance testing was applied to test the aerosol delivery performance for Friars' Balsam, and its key chemical constituent, benzoic acid (BA). RESULTS: A respirable dose of 59.9 ± 9.0 µg of BA was aerosolized in a 10 minutes period from a dose of 3.3 mL Friars' Balsam (equivalent to 35.1 ± 0.2 mg of BA) in 375 mL of steaming water using the glass twin stage impinger at a flow rate of 60 L·min-1. The respirable dose from a standardized aqueous BA inhalation formulation increased from 115.9 ± 10.6 to 200.2 ± 19.9 µg by increasing the simulated inhalation period from 5 to 10 minutes. When tested with a simulated inhalation maneuver (500 mL tidal volume, 13 minutes-1 respiration rate, 1:2 inspiratory:expiratory ratio) a respirable dose of 112.8 ± 40.3 µg was produced. CONCLUSIONS: This work has highlighted the potential for aerosol drug delivery using steam inhalers that are popular with patients. Physicians should therefore be aware of the potential for lung dosing with irritants when patients self-medicate using the Nelson Inhaler with vaporizing formulations such as Friars' Balsam.

The History of Therapeutic Aerosols: A Chronological Review.

In 1956, Riker Laboratories, Inc., (now 3 M Drug Delivery Systems) introduced the first pressurized metered dose inhaler (MDI). In many respects, the introduction of the MDI marked the beginning of the modern pharmaceutical aerosol industry. The MDI was the first truly portable and convenient inhaler that effectively delivered drug to the lung and quickly gained widespread acceptance. Since 1956, the pharmaceutical aerosol industry has experienced dramatic growth. The signing of the Montreal Protocol in 1987 led to a surge in innovation that resulted in the diversification of inhaler technologies with significantly enhanced delivery efficiency, including modern MDIs, dry powder inhalers, and nebulizer systems. The innovative inhalers and drugs discovered by the pharmaceutical aerosol industry, particularly since 1956, have improved the quality of life of literally hundreds of millions of people. Yet, the delivery of therapeutic aerosols has a surprisingly rich history dating back more than 3500 years to ancient Egypt. The delivery of atropine and related compounds has been a crucial inhalation therapy throughout this period and the delivery of associated structural analogs remains an important therapy today. Over the centuries, discoveries from many cultures have advanced the delivery of therapeutic aerosols. For thousands of years, therapeutic aerosols were prepared by the patient or a physician with direct oversight of the patient using custom-made delivery systems. However, starting with the Industrial Revolution, advancements in manufacturing resulted in the bulk production of therapeutic aerosol delivery systems produced by people completely disconnected from contact with the patient. This trend continued and accelerated in the 20th century with the mass commercialization of modern pharmaceutical inhaler products. In this article, we will provide a summary of therapeutic aerosol delivery from ancient times to the present along with a look to the future. We hope that you will find this chronological summary intriguing and informative.

Historical estimation of carbonaceous aerosol emissions from biomass open burning in China for the period 1990-2005.

Multi-year inventories of carbonaceous aerosol emissions from biomass open burning at a high spatial resolution of 0.5° × 0.5° have been constructed in China using GIS methodology for the period 1990-2005. Black carbon (BC) emissions have increased by 383.03% at an annual average rate of 25.54% from 14.05 Gg in 1990 to 67.87 Gg in 2005; while organic carbon (OC) emissions have increased by 365.43% from 57.37 Gg in 1990 to 267.00 Gg in 2005. Through the estimation period, OC/BC ratio for biomass burning was averagely 4.09, suggesting that it was not the preferred control source from a climatic perspective. Spatial distribution of BC and OC emissions were similar, mainly concentrated in three northeastern provinces, central provinces of Shandong, Jiangsu, Anhui and Henan, and southern provinces of Guangxi, Guangdong, Hunan and Sichuan basin, covering 24.89% of China's territory, but were responsible for 63.38% and 67.55% of national BC and OC emissions, respectively.

A brief history of gamma scintigraphy.

Gamma scintigraphy involves the radiolabeling of inhaled drug formulations, followed by in vivo imaging of deposition in two dimensions. This permits whole lung deposition to be quantified as mass of drug or percentage of the dose, and regional deposition patterns to be assessed. Gamma scintigraphy is the method by which the majority of inhaled drug deposition data have been obtained, and scintigraphic studies have become viewed as milestone assessments in the development of new pulmonary drug products. Lung deposition data are used to show "proof of concept" in vivo for these products, and act as a bridge between in vitro laboratory testing and a clinical trials program. Gamma scintigraphy is likely to remain the method of choice for assessing inhaled drug deposition for some time to come.

A history of nebulization.

The simplest and most natural route of drug delivery to the lungs is the inhaled one. From the historical and medical point of view, it was a Greek, Pedanus Discorides, the father of the science of pharmacy, who, during the first century prescribed inhaled fumigation. Pipes were also used to inhale hallucinogenic substances. All shamans knew the psychotropic effects of poisonous plants such as Datura stramonium, especially Red Indians, in their peace calumets; but Indians of Madras used fumigations of Datura ferox to treat asthma. Since 1803, this therapeutic was imported in Great Britain and cigarettes with leaves of datura were used by asthmatics until 1992. In the middle of the nineteenth century, to treat grapevines diseases and in response to the fashion of inhaling thermal waters, spray technology was developed for the effervescent waters at the thermal spas. The onslaught of tuberculosis, similar to AIDS a century later, brought back into practice the inefficacious use of antiseptic aerosol therapy. With the discovery of adrenaline, ephedrine aerosols enjoyed a rebirth. The perfecting of jet nebulizers by R. Tiffeneau, father of FEV1 and M.B. Wright, father of peak-flow, allowed a better practice of inhalotherapy. In 1949, the United States, ultrasonic nebulizers made their first appearance in the form of humidifiers, but doctors were quick to add medications to produce therapeutic aerosols. After 150 years, with the improvement of nebulizer systems and new nebulized medications, the nebulization story is still not concluded.