COVID-19 presenting with spontaneous massive pneumomediastinum in a three-month-old child.

A three-month-old child presented to our district general hospital with acute respiratory distress. He was found to have massive spontaneous pneumomediastinum and extensive surgical emphysema overlying the neck. Tracheal intubation using the GlideScope® was difficult, and the patient's trachea was ultimately intubated with a direct laryngoscope. Computed tomography revealed bilateral lung consolidation and reverse transcriptase-polymerase chain reaction swab was positive for SARS-CoV-2. There was no other precipitating factor to explain the presence of pneumomediastinum. The patient was treated with pleural and mediastinal drains, required five days of mechanical ventilation on a paediatric intensive care unit and subsequently made a full recovery. We outline our initial differential diagnosis, airway management plan, and propose a mechanism for the development of spontaneous pneumomediastinum in this case. We suggest that clinicians should consider pneumomediastinum as a potential cause of surgical emphysema, particularly in the context of COVID-19, even in infants. To our knowledge, this is the first reported case of COVID-19 in this age group with spontaneous pneumomediastinum as the presenting feature.

Nonneoplastic changes in the olfactory epithelium--experimental studies.

Interest in the olfactory mucosa has increased in recent years, since it has been shown to possess a considerable amount of cytochrome P-450-dependent monooxygenase activity and a wide variety of chemicals have been identified as olfactory toxins. Many chemicals induce lesions of a general nature in the olfactory mucosa, i.e., inflammation, degeneration, regeneration, and proliferation, whereas others cause more specific effects. Changes in the olfactory mucosa with reference to chemicals that initiate them are reviewed in this paper. Studies with 3-trifluoromethyl pyridine (3FMP) illustrate some of these general changes and show the importance of examining the olfactory mucosa at early time periods. The earliest damage seen by light microscopy was 6 hr after a single inhalation exposure to 3FMP, and by day 3, early regenerative changes were observed. Changes were seen by electron microscopy 30 min after an oral dose, and the primary site of toxicity appeared to be the Bowman's glands. Although atrophy of nerve bundles in the lamina propria would be the expected consequence of severe necrosis of the sensory cells, this is not always the case. Exposure to irritants such as acetaldehyde, formaldehyde, and dimethylamine results in nerve bundle atrophy, but with chemicals such as 3FMP, 3-methylindole, and 3-methylfuran--which are activated by mixed-function oxidases--the nerve bundles remain intact. Future work, including metabolism studies, will provide information on the mode of action of these chemicals.

Methyl methacrylate toxicity in rat nasal epithelium: investigation of the time course of lesion development and recovery from short term vapour inhalation.

An investigation of the time course of development and recovery of the nasal lesion induced in rats by inhalation of methyl methacrylate (MMA) was conducted. Groups of 45 female F344 rats (five animals per time point) were exposed whole body for 6 hours per day to 0 (control), 110 or 400 ppm MMA for 1, 2, 5, 10 or 28 consecutive days. Additional animals were retained for a period of 4, 13, 24 or 36 weeks following exposure to assess reversibility of any nasal tissue effects. After inhalation of MMA there was damage to the olfactory epithelium at 110 and 400 ppm. This was apparent following the first day of exposure, but recovery/regeneration was evident during the subsequent days of the exposure phase of the study. The most severely affected section of the nasal passages was that which included the ethmoturbinates. Focal adhesions between the septum and turbinates and between the turbinates themselves were seen in some animals exposed to 400 ppm MMA at time points after 5 days of exposure. There were no lesions in the squamous, transitional or respiratory epithelia and none in control rats. Lesions that developed in rats exposed to 110 ppm MMA subsequently repaired during the exposure period. At 400 ppm, the majority of the olfactory epithelium had returned to normal within 13 weeks of the end of the exposure phase, but minimal respiratory metaplasia remained evident and there were some focal adhesions between the septum and turbinates and between the turbinates themselves.

Olfactory and hepatic changes following inhalation of 3-trifluoromethyl pyridine in rats.

Rats exposed by inhalation to 3-trifluoromethylpyridine (3-FMP) for 10, 30 or 90 days showed an unusual response in the nasal passages. Focal histological change including reduction in the number of cell layers, disorganisation, vacuolation and minimal necrosis was confined to the olfactory epithelium. Axon bundles and the olfactory bulb were unaffected but there was loss of PAS staining affinity in Bowman's glands. The onset of the lesion showed a very steep dose-relationship approximating a quantal response; no effects were seen after 90 days exposure to 0.1 ppm but the changes were fully developed after 30 days exposure to 0.5 ppm. There was no marked progression with either increased exposure concentrations (up to 329 ppm) or with increased duration of exposure (10-90 days). The respiratory epithelium was generally unaffected apart from a mild irritant response seen only after 90 days. Exposures also resulted in a response in the liver. Centrilobular and midzonal vacuolation was observed at 10 and 30 days following exposures at or above 5 ppm 3-FMP and the severity increased with concentration. The lesion regressed with time even when exposure continued and only minimal changes were evident after 90 days, probably indicating an adaptive response. This work demonstrates the high organ specificity of 3-FMP, particularly for the olfactory epithelium.

Olfactory and hepatic changes following a single inhalation exposure of 3-trifluoromethyl pyridine in rats: concentration and temporal aspects.

The effects of a single exposure to 3-trifluoromethyl pyridine (3FMP), were investigated in two studies. In the first study, rats were exposed nose only to 0, 50 or 800 ppm 3FMP for periods of 15 min to 4 h. Half were sacrificed on day 3 and the remainder on day 10. In the second study, rats were exposed whole body to 0, 0.1, 1.0, 10 or 50 ppm 3FMP for 6 h, with sacrifices immediately after exposure (6 h), 24 h and on days 3 (48 h after exposure started) 5, 8, 11, 35, 70 and 157. Effects were seen in the olfactory epithelium at concentrations of 1 ppm and above and in the liver at concentrations of 50 ppm and above. In the olfactory epithelium the earliest changes were seen immediately after exposure and by 24 h this progressed to extensive necrosis with sloughing of the epithelium. By day 3, the epithelium was replaced by undifferentiated basophilic cells, considered to reflect early regeneration. Regeneration progressed to complete recovery between days 70 and 157, no changes were seen in the nasal respiratory epithelium, an olfactory function test on rats exposed for 6 h to 50 or 10 ppm 3FMP showed a reduced sense of olfaction at days 3 and 5 with complete recovery on subsequent days, indicating functional recovery in advance of histological normality. Single cell necrosis was seen in the liver at day 3 after 30 min exposure and immediately after 6 h exposure to 50 ppm 3FMP. At 24 h after a 6 h exposure to 50 ppm this had progressed to necrosis, haemorrhage and moderate cytoplasmic hepatocyte vacuolation in centrilobular areas. The lesion had completely recovered by day 5.

Effects of long term inhalation of alumina fibres in rats.

Groups of rats were exposed by inhalation to atmospheres containing a refractory alumina fibre (Saffil Fibres, I.C.I.) either as manufactured or in a thermally aged form. Similar groups were exposed to UICC chrysotile A asbestos or clean air to serve as positive and negative controls respectively. Exposures continued for 86 weeks after which the animals were maintained to 85% mortality. Pulmonary reaction to both forms of alumina fibre was minimal; chrysotile asbestos provoked the expected progressive fibrosis. Pulmonary tumours (both benign and malignant) were confined to rats dosed with asbestos. The results support the predicted inert nature of these alumina fibres.

Olfactory toxicity of methyl iodide in the rat.

The monohalomethanes (methyl iodide, methyl bromide and methyl chloride) are widely used industrial methylating agents with pronounced acute and chronic toxicity in both experimental animals and man. Recently inhalation exposure of rats to methyl bromide has been shown to result in severe olfactory toxicity. This study examined the effects on the rat nasal cavity of inhalation of methyl iodide (100 ppm for 0.5-6 h), and demonstrated that methyl iodide is a more potent olfactory toxin than methyl bromide. Within the nasal cavity the olfactory epithelium was the principle target tissue, and it was only at high doses (600 ppm.h) that limited damage to transitional epithelium occurred. The squamous and respiratory epithelia were consistently unaffected. Within olfactory epithelium the sustentacular cells were the primary cellular target and damage to sensory cells appeared to be a secondary event. Methyl iodide induced olfactory damage was reversible, and 2 weeks after exposure almost complete repair had taken place.

The role of glutathione S-transferase- and cytochrome P450-dependent metabolism in the olfactory toxicity of methyl iodide in the rat.

The aim of this study was to investigate the role of metabolic activation in the olfactory toxicity of methyl iodide (MeI). Adult male rats were exposed via nose-only inhalation to 100 ppm MeI for 0-6 h, and non-protein sulphydryl (NP-SH) concentrations determined in selected tissues. Depletion of NP-SH occurred in all tissues, but was most marked and rapid in the respiratory epithelium of the nasal cavity and the kidney. Olfactory, lung and liver NP-SH levels were affected to a lesser extent, and those of the brain declined by only 20-30% over the whole time course. In order to modulate glutathione (GSH) status, animals were pre-treated with (1) phorone plus L-buthionine sulphoximine (BSO), which depleted NP-SH levels in all the tissues examined, or (2) the isopropyl ester of GSH (IP-GSH), which was shown to replenish NP-SH concentrations in all tissues except the liver of animals previously administered phorone. When animals were pre-treated with phorone plus BSO and then exposed to 100 ppm MeI for 2 h, there was a potentiation of the toxicity of MeI as judged by the clinical observations on the animals. In contrast, treatment with IP-GSH prior to and during exposure to MeI for 4 h afforded a marked protection to the olfactory epithelium. In order to inhibit cytochromes P450, animals were pre-treated with cobalt protoporphyrin IX. This decreased hepatic cytochrome P450 concentrations by > 90%, but when animals were then exposed to 100 ppm MeI for 4 h there was no effect on the severity of the olfactory lesion. These results indicate that conjugation of MeI with GSH is a detoxification rather than an activation pathway. Also, there is no major role for cytochrome P450-dependent oxidation in the development of the olfactory lesion.