Per Camner

The immotile-cilia syndrome. A congenital ciliary abnormality as an etiologic factor in chronic airway infections and male sterility.

We investigated six men and a woman suspected of suffering from congenital immotility of cilia. All had chronic airway infections, and the men had immotile spermatozoa. The woman and three men had Kartageners syndrome. The investigations included measurements of the mucociliary transport in the lower airways and ultrastructural studies of the sperm tails or respiratory cilia (or both). Mucociliary transport was significantly delayed. Sperm tails lacked dynein arms in five patients. Respiratory cilia from the women and two men lacked dynein arms and were irregularly oriented. The results support the hypothesis that a congenital defect in the cilia and sperm tails will cause chronic respiratory-tract infections and male sterility--the immotile-cilia syndrome. In about half these patients there will also be a situs inversus--i.e., Kartageners syndrome.

A Comparison of Nasal and Tracheobronchial Clearance

Tracheobronchial clearance and nasal clearance were compared in 13 pairs of monozygotic twins and 11 nontwins. Tracheobronchial clearance was studied by having the subjects inhale, by mouth, a test aerosol of 6μmol particles tagged with technetium Tc 99m (99mTc) and making external measurements of the radioactivity. Nasal clearance was studied with two methods: (1) a 0.6-mm anion resin particle tagged with 99mTc was externally followed at five different points along the nasal passage and (2) a saccharine particle was placed on the mucociliary mucosa anteriorly in the nose and the time was registered until the subject noted a sweet taste. A weak positive association existed between tracheobronchial clearance and nasal clearance as studied with the saccharine particle method, but no association was found between tracheobronchial clearance and nasal clearance as tested by the tagged resin particle method.

Increased Mucociliary Transport by Cholinergic Stimulation

Tracheobronchial clearance of inhaled 6mum Teflon particles (density 2 gm/cu cm) tagged with technetium 99m was studied in healthy subjects by external measurement of the radioactivity in the lungs for two hours. Clearance, salivary secretion, blood pressure, and heart rate were determined in eight subjects after double-blind, subcutaneous administration of 0.25 mg terbutaline sulfate, a beta-adrenoceptor stimulating compound and vehicle, respectively, in a crossover study. Terbutaline produced a marked increase in clearance and a slight increase in heart rate, but had no important effect on salivary secretion or blood pressure. The result indicates that the blood concentrations of catecholamines might be of importance for the regulation of the mucociliary transport rate.

Human Lung Deposition of Particles Suspended in Air or in Helium/Oxygen Mixture

Deposition in mouth and throat and the fraction of alveolarly deposited particles in the lung of 3.6- to 3.8-microns Teflon particles labeled with 99mTc were estimated in nine healthy subjects. The particles were inhaled in air or helium/oxygen mixture with a flow of 0.5 l/s by subjects with or without induced bronchoconstriction. The bronchoconstriction (two- to threefold increase in airway resistance) was induced by an aerosol of methacholine bromide. As the Reynolds number is three times lower for the helium/oxygen mixture than for air, and the sedimentation rate of the particles is about the same in both, a different regional deposition between particles suspended in air and helium/oxygen mixture should be due to turbulence. Deposition in mouth and throat did not differ significantly between air and the helium/oxygen mixture. The alveolarly deposited fraction tended to be larger for unconstricted airways and was significantly larger for constricted airways for inhalations in the helium/oxygen mixture compared to air. In real life, air pollutants and therapeutic aerosols may be inhaled with larger flow rates and broncho-constriction may be more pronounced in patients, so that deposition of particles due to turbulence can be important.

Dissolution of metals by human and rabbit alveolar macrophages.

The ability of human and rabbit alveolar macrophages to dissolve 0.1-0.5 micron MnO2 particles in vitro was compared. The amount of Mn added and dissolved from the particles over periods of nought, one, and three days was determined by flame atomic absorption spectrophotometry. The amount dissolved by human and rabbit macrophages was similar; on average 43.1% and 43.9%, respectively, were dissolved within three days. But rabbit and human macrophages dissolved significantly more Mn than was dissolved in the respective culture medium without macrophages after one and three days. It is suggested that the dissolution of particles by alveolar macrophages should be one basic component in any model of alveolar clearance of inorganic particles.

Ability of rabbit alveolar macrophages to dissolve metals.

Manganese dioxide particles, 0.1-0.5 micron, were added to samples of 2-3 X 10(6) rabbit alveolar macrophages. The amount of manganese added and dissolved from the particles, over periods of 0, 1, 3, and 5 days, was determined by flame atomic absorption spectrophotometry. Macrophages from six rabbits received about 10 micrograms of Mn, macrophages from two rabbits about 30 micrograms, and macrophages from another two rabbits about 100 micrograms. Over periods of 1, 3, and 5 days the macrophages in all three dose groups dissolved two to three times more Mn than was dissolved in control experiments. In control experiments solubility was studied in the medium without macrophages. Macrophages cultivated 3 days before the addition of MnO2 dissolved the particles within another 2 days to an extent similar to that in the control experiments. The ability of the macrophages to dissolve MnO2 particles might be related to the low pH values in the phagosomes. Studies of the ability of macrophages from various species to dissolve metal particles as well as of pH values in their phagosomes might lead to a better understanding of alveolar clearance of metal particles.

On the Function of Cilia in the Female Reproductive Tract

A recently discovered syndrome is characterized by congenital immotility of the cilia. It consists of chronic infections in the respiratory system, male infertility, and, in about one-half of the cases, situs inversus. The syndrome thus includes Kartageners syndrome. The syndrome provides a unique opportunity to gain insight into the role of the cilia in the human body. Five women evidently suffering from this syndrome were examined. They had no gynecologic disorders. Three of the five women had tried to become pregnant and two have suceeded. A review of the literature indicates that men with Kartageners syndrome are usually infertile, whereas the women are not. This fact and the data presented herein constitute strong evidence that ciliary motility is not essential for female fertility. More conclusive proof could be obtained if any of the affected women would consent to ultrastructural investigation of the oviductal cilia.

Deposition of Large Particles in Human Lung

Twenty-four nonsmoking males, all without history of pulmonary disease, were randomly divided into four groups of six subjects each. The subjects in each group inhaled monodisperse Teflon particles labelled with 111In (half-life 2.83 days); 8.2, 11.5, 13.7 and 16.4 micron aerodynamic diameter, respectively. Radioactivity in head and throat, lung and stomach was determined after 0, 3 and 24 hrs using a profile scanner. For some subjects radioactivity was also determined using a whole-body scanner at 3.5 and 24 hrs. After the 24-hr determination the subjects inhaled labelled Teflon particles again, this time with a filter in front of the mouth. Average values for total deposition in the body, obtained using a profile scanner, whole-body scanner and filter measurements, agreed fairly well. Lung retention values obtained by whole-body and profile scanning also agreed well. The average deposition in the lung, expressed as a percentage of total deposition, was 49, 31, 21 and 13% for the four particle sizes (8.2-16.4 micron). Alveolar deposition, determined as retention at 24 hrs and expressed in percent of total deposition, was 15, 4, 4 and 1%. For the smallest particle sizes the deposition values agreed with earlier investigations. However, for the larger particles the two deposition values were higher than expected when compared to earlier studies.

Alveolar macrophages in rabbits exposed to nickel dust. Ultrastructural changes and effect on phagocytosis.

Abstract Two groups of four rabbits each were exposed to 0.5 and 2.0 mg/m 3 of metallic nickel dust respectively, for 4 weeks (5 days/week, 6 hours/day). About half of the particle masses penetrated a Casella preseparator. After exposure the lungs were extracted and lavaged. Compared to four control rabbits significant effects were seen in both exposed groups with regard to lung weight and density as well as phagocytic activity, size distribution, and ultrastructure of the alveolar macrophages (numerous slender microvilli and long protrusions from the cell surface and laminated structures similar to those seen in alveolar type II cells). The effects on the macrophages were probably not caused directly by nickel. The lung washing from the exposed rabbits contained an amorphous substance rich in phospholipids and laminated structures. Apart from the ultrastructural changes the effects seemed to be dose related. The results of exposure to metallic nickel dust have at least some features in common with “alveolar lipoproteinosis,” described in rats exposed to silica dust, and with “pulmonary alveolar proteinosis,” described in man.

Human Deposition and Clearance of 6-μm Particles Inhaled with an Extremely Low Flow Rate

In human experimental data, tracheobronchial deposition reaches its maximum for particles of about 6 microns inhaled at 0.5 L/s. The purpose of the present study was to investigate if tracheobronchial deposition of 6-microns particles could be increased, especially in the smaller bronchi, using an extremely slow inhalation rate. Six healthy nonsmokers inhaled monodisperse 6-microns (aerodynamic diameter) Teflon particles labeled with 111In at 0.04 L/s. Radioactivity in mouth and throat, lung, and stomach was measured immediately after inhalation by profile scanning and in the lung also after 24, 48, 72, and 96 h. There was a substantial clearance between 24 and 72 h; around 20% of the total clearance occurred between 24 and 72 h. This is in contrast to earlier studies in which only around 1% of 6-microns particles inhaled at 0.5 L/s cleared between 24 and 72 h. This indicates a markedly higher deposition in the smaller bronchi at 0.04 L/s than at 0.5 L/s. The total tracheobronchial deposition was 50%, compared to about 30% when particles were inhaled at 0.5 L/s. These findings could be therapeutic use. They also implicate the possibility of developing a diagnostic model that can separate between bronchial reactivity in large and small bronchi.